Epidemiological evidence suggests that bisphosphonates are the most promising drugs for patients with osteogenesis imperfecta (OI). However, data on this issue are controversial. We conducted a meta-analysis to assess the efficacy of bisphosphonates on bone mineral density (BMD) and fracture rate in patients with OI. Electronic databases were searched to find relevant studies. Two reviewers independently identified relevant randomized controlled trials, which evaluated the efficacy of bisphosphonates in patients with OI. Outcome measures were fracture incidence and BMD changes in different skeletal sites. A total of 9 randomized controlled trials including 557 patients were identified. Meta-analysis demonstrated a beneficial effect of bisphosphonates on spine BMD Z-score and area BMD (in grams per square centimeter)%. Patients treated with bisphosphonates had a lower risk of fracture [risk ratio (RR)= 0.80; 95% confidence interval (CI): 0.66–0.97] compared with those in control groups. In children, bisphosphonates were efficacious in reducing fractures (RR= 0.80; 95% CI: 0.66–0.97), where in adults, bisphosphonates seemed equivalent to placebo in that respect (RR= 0.82; 95% CI: 0.42–1.59), although no significant difference was noted between these 2 RRs (test of interaction, z=− 0.07; P= 0.94). There was also no significant difference in reducing fractures between oral and intravenous bisphosphonates (P= 0.23). This study showed that bisphosphonates could increase the BMD and reduce the risk of facture in patients with OI. There was no enough evidence to identify any differences in efficacy between oral and intravenous bisphosphonates on fracture reduction, as well as between children and adults.