Purpose: To investigate the biomechanical, histological, and radiological effects of sildenafil and pentoxifylline on femoral fracture healing in rats. Methods: Forty-eight Sprague-Dawley rats were divided into three groups equally according to the pharmacological agents to be investigated. Femoral shaft fractures were formed in the left side. Group 1 (control group), group 2, and group 3 were administered with saline, sildenafil, and pentoxifylline during the fracture healing process, respectively. Eight rats from each group were euthanized on days 15 and 30. X-ray images of the rats were taken after euthanasia for radiographical examination. Femur samples were subjected to histopathological and biomechanical (three-point bending) examinations. Results: Radiologically, no difference between the Goldberg scores of the groups was found for day 15 (p > 0.05), while higher Goldberg scores were obtained from group 2 than that of group 1 (p > 0.05) and group 3 (p < 0.05) for day 30. In the biomechanical analysis, higher mean breaking forces were found both for day 15 and day 30 from group 2 than those obtained from group 1 (for day 15 p > 0.05 and day 30 p > 0.05) and group 3 (for day 15 p < 0.05 and day 30 p < 0.01). Higher mean absorbed energy values were obtained from group 2 than those obtained from group 1 (for day 15 p > 0.05 and day 30 p < 0.05) and group 3 (for day 15 p < 0.01 and day 30 p < 0.01). A significant difference was not found between the histological scores of all groups (p > 0.05) for day 15, while the histological score of group 1 on day 30 was found to be significantly lower than that of sildenafil and pentoxifylline groups (p < 0.05). Conclusion: Sildenafil had a positive effect on fracture healing, while pentoxifylline did not provide consistent positive effect.