The use of dental implants for the rehabilitation of edentulous areas is an established treatment, showing high success rates. Primary stability is one of the pre-requisites for osseointegration, and it is ensured by the mechanical interlocking at the bone to implant interface. Current procedures have changed from the original protocols, towards a reduction of treatment time. Nowadays, the achievement of a great magnitude of primary stability is demanded in clinical practice, since there is a trend to load the implant immediately or in the early stages after implant insertion. Aiming on this, several modifications have been introduced, such as more aggressive implant design, modified surfaces and novel surgical techniques. Undersized drilling preparation is one of the most commonly adopted protocols during the implant surgery. This technique creates an osteotomy that is consistently smaller than the implant diameter, so that a tight interfacial contact and compression is created. Clinically this is perceived with an increase of the insertion torque value (ITV). Albeit commonly performed, several aspects of undersized drilling are still not well investigated. It was hypothesized that a great magnitude of compression at the implant insertion would generate tissue damage and may trigger a negative bone response during the healing time. This could lead to an impairment of bone material properties, a decrease of stability and marginal bone loss. Based on a clinical need, the general aim of this thesis was a more consistent understanding of the effects of an undersized drilling osteotomy. Study I aimed to provide the current evidence based on the literature on biomechanical, biologic and clinical outcomes. An electronic and a manual search were undertaken including in vitro, animal, and clinical studies in which an undersized drilling protocol was compared with a non-undersized drilling protocol. 29 studies met the inclusion criteria, including 14 biomechanical, 7 biologic, 6 biologic and biomechanical, and 2 clinical. A meta-analysis was not performed. Several studies showed that implants inserted with an undersized drilling approach reached a significantly higher ITV than conventional drilling in low-density substrates, while this effect is less evident in denser substrates. Similar long-term bone-toimplant contact (BIC) was achieved between implants inserted with undersized and non-undersized protocols. Results in the short term were inconclusive. Clinical studies did not show negative outcomes for undersized drilling in low-density bone, although clinical evidence was sparse. In study II, clinical outcomes were evaluated with a retrospective design, which included 87 patients treated with 188 implants inserted with an adapted drilling protocol according to the surgeon’s perception of bone quality. ITV and Marginal bone loss (MBL) between implant placement and permanent restoration was calculated. ITV differed significantly based on mandible/maxilla, bone quality, implant diameter, and drilling protocol. Median MBL was 0.05 mm (0.00; 0.24). A significant difference was found between the mandible and maxilla and between drilling protocols. In particular, significantly higher MBL was found in the undersized drilling protocol. Multiple regression models were built to test the effect of independent variables on the outcomes. ITV was influenced by bone quality and implant diameter. MBL was influenced by bone quality, implant diameter, ITV, and the interaction between bone quality and ITV. It was estimated that MBL was greater with increased bone density and ITV. Study III aimed to evaluate in vivo the extent of cortical bone remodeling and the bone integration of implants placed after different drilling protocols. Forty-eight implants were inserted into the sheep mandible following two drilling protocols: undersized preparation and non‐undersized preparation. Healing time was set at 5 and 10 weeks. Removal torque (RTQ) was measured and the peri-implant bone was scanned using a micro-computed tomography (μ‐CT). Bone volume density (BV/TV) was calculated in pre‐determined hollow cylinders. Total BIC and newly‐formed BIC (newBIC) and Bone Area Fraction Occupancy (BAFO) was measured. Results showed that, at 5 weeks of healing, significantly greater RTQ value was present for the undersized group, while non-undersized group presented greater values of BV/TV, newBIC and BAFO. No differences were noted at 10 weeks. The purpose of study IV was to assess bone material properties and to predict the strain/stress distribution on cortical bone using a multiscale in silico model. Two types of micro-scale bone structures were assessed: cortical bone models with resorption cavities and without resorption cavities, following undersized and non-undersized drilling protocols respectively. In a macro-scale model, oblique load of 100N was simulated. Maximum principal stress/strain, and shear stress/ strain were calculated. Bone with resorption cavities presented anisotropic material properties. Compared to bone without cavities, greater maximum values of Maximum principal stress/strain was calculated, both in macro- and micro-scale models. These values were located at the implant neck area and in the proximity of cavities respectively. Greater values of shear stress/strain were found in the test along the mandibular longitudinal plane. In summary, this thesis suggested that undersized drilling technique can cause negative effects in the cortical bone. The literature indicated that undersized drilling technique is effective in increasing the ITV in low-density bone. However, ITV is mostly influenced by bone quality, rather than drilling protocol. Furthermore, high ITV can induce greater bone resorption in dense bone. Cortical bone has the capability to maintain high levels of rotational stability at undersized sites in the early phases of healing, despite the great amount of micro-damage. From a biologic point of view, this procedure causes a reduced apposition of newly formed bone at the interface and it initiates an intense bone resorption activity in the surrounding tissue. This creates a temporary porosity into cortical bone, reducing the volume of peri-implant mineralized tissue. Intra-cortical resorption cavities caused an impairment of material properties and compromised mechanical behavior. This bone model is more prone to micro-damage and to a delayed healing process. Therefore, avoiding early loading protocols is recommended. Future clinical studies should focus on the longer-term outcome of undersized drilling, since the current clinical evidence is insufficient.