Study Design. Animal model. Objective. To determine whether aminocaproic acid (Amicar) and tranexamic acid (TXA) inhibit spine fusion volume. Summary of Background Data. Amicar and TXA are antifibrinolytics used to reduce perioperative bleeding. Prior in vitro data showed that antifibrinolytics reduce osteoblast bone mineralization. This study tested whether antifibrinolytics Amicar and TXA inhibit spine fusion. Methods. Posterolateral L4-L6 fusion was performed in 50 mice, randomized into groups of 10, which received the following treatment before and after surgery: (1) saline; (2) TXA 100 mg/kg; (3) TXA 1000 mg/kg; (4) Amicar 100 mg/kg; and (5) Amicar 1000 mg/kg. High-resolution plane radiography was performed after 5 weeks and micro-CT (computed tomography) was performed at the end of the 12-week study. Radiographs were graded using the Lenke scale. Micro-CT was used to quantify fusion mass bone volume. One-way analysis of variance by ranks with Kruskal-Wallis testing was used to compare the radiographical scores. One-way analysis of variance with least significant difference post hoc testing was used to compare the micro-CT bone volume. Results. The average +/- standard deviation bone volume/total volume (%) measured in the saline, TXA 100 mg/kg, TXA 1000 mg/kg, Amicar 100 mg/kg, and Amicar 1000 mg/kg groups were 10.8 +/- 2.3%, 9.7 +/- 2.2%, 13.4 +/- 3.2%, 15.5 +/- 5.2%, and 17.9 +/- 3.5%, respectively. There was a significant difference in the Amicar 100 mg/kg (P < 0.05) and Amicar 1000 mg/kg (P < 0.001) groups compared with the saline group. There was greater bone volume in the Amicar groups compared with the TXA group (P < 0.001). There was more bone volume in the TXA 1000 mg/kg group compared with TXA 100 mg/kg (P < 0.05) but the bone volume in neither of the TXA groups was different to saline (P = 0.49). There were no between-group differences observed using plane radiographical scoring. Conclusion. Amicar significantly "enhanced" the fusion bone mass in a dose-dependent manner, whereas TXA did not have a significant effect on fusion compared with saline control. These data are in contrast to prior in vitro data that antifibrinolytics inhibit osteoblast bone mineralization.