The most effective method to prevent and treat bone loss following hematopoietic stem cell transplantation (HSCT) remains uncertain. We conducted a comprehensive search in four electronic databases until August 2015. We retrieved articles describing patients with bone loss or fractures who received HSCT. Controlled trials, with a follow-up period of at least 12 months, were included. Twelve studies (19 publications) met our inclusion criteria. A total of 643 participants underwent HSCT (85.7% allogeneic HSCT). There was a statistically significant lower mean bone mineral density (g/cm2) percentage change of the lumbar spine (mean difference (MD) 7.8, 95% confidence interval (CI) 5.6-10.0) and femoral neck (MD 6.7, 95% CI 5.6-7.9) in the bisphosphonate therapy group compared with the control group with no bisphosphonate therapy at 12 months. In a subgroup analysis, seven different comparison groups were evaluated. The rate of fractures or X-ray findings of subclinical vertebral fractures was similar between groups. Bisphosphonates are promising in the prevention and treatment of bone loss following HSCT. Additional research is required to determine whether they reduce long-term fracture risk.