Aims: To evaluate the predictive potential of preoperative psychological and psychophysiological variables in estimating severity of postoperative pain following mandibular third molar surgery (MTMS). Methods: Following ethical committee approval and informed consent, 40 consecutive patients scheduled for MTMS were included. Preoperative psychometric indicators of anxiety, depression, and vulnerability were evaluated by patient questionnaires. Thermal thresholds and heat pain perception (1 second phasic stimuli: 44°C to 48°C) were evaluated with quantitative sensory testing techniques. Standardized surgery was performed during local anesthesia. Postoperative pain management was with rescue paracetamol and ibuprofen. The patients were instructed to record each day their pain at rest and during dynamic conditions, and their requirement of analgesics for 14 days following surgery. Results: Thirty-eight patients completed the study. Eight patients were readmitted because of pain. During the postoperative period, one or more episodes of moderate to severe pain (> 30 on a visual analog scale) was reported by 60% (23/38) at rest, 63% (24/38) during mouth-opening, and 73% (28/38) during eating. In a multiple regression model, the combination of psychological vulnerability and heat pain perception rendered a predictive model that could account for 15 to 30% of the variance in postoperative pain during resting and dynamic conditions (P = .03 to .001).Conclusion: Implementation of clinically relevant preoperative screening methods may offer more efficacious postoperative pain therapies to pain-susceptible individuals undergoing mandibular third molar surgery.