Abstract Background This study was to evaluate the effects of repetitive brief ischemia (RBI) on bone healing in patients with tibial shaft fractures. Methods In this prospective clinical trial, patients with tibia shaft fractures were enrolled between January 2016 and January 2021. The intermittent pneumatic compression (IPC) device was used to make RBI on the affected limb after surgical operation 24 h. The inflation pressure was the systolic pressure of patients + 50 mmHg. Patients were received 30 s inflation/30 s deflation 30 times twice a day for 4 weeks. The primary outcome was bone healing time and the secondary outcomes were the rates of delayed union and nonunion, the rates of venous thrombosis of lower limbs, Johner-Wruhs scores, Lysholm knee score, VAS scores, postoperative complications, serum BMP-2, osteocalcin (OC) and bone specific alkaline phosphatase (BS-ALP). Results A total of 32 patients were enrolled finally and all were completed with a 12 months follow-up. All the fractures were healed and the bone healing time was 3(1) months in RBI group. However, the bone healing time of control group was 4(1) and there was statistical difference between the two groups (p