OBJECTIVES Conduct a systematic review and meta-analysis of published literature on persistence with denosumab in patients with osteoporosis. METHODS A systematic review identified retrospective and prospective observational studies reporting 12-, 18-, or 24-month persistence with denosumab, an osteoporosis therapy approved in 2010. Searches covered the period January 2011─May 2014 and were conducted in the PubMed and EMBASE databases, and conference abstract supplements from ACR, AMCP, ASBMR, WCO-IOF-ESCEO, and ISPOR. To be eligible, studies needed to report at least one estimate of persistence with denosumab in patients with osteoporosis, have a clear definition of persistence, and be in English language. Using a random effects model, pooled estimates of denosumab persistence were calculated for retrospective and prospective studies separately. A subgroup analysis was conducted based on geographical regions. RESULTS The search identified 338 unique citations in PubMed and EMBASE, and 200 conference abstracts. After applying the eligibility criteria, 11 studies were included in the final review and meta-analysis (7 retrospective; 4 prospective). All studies reported at least one estimate of 12-month persistence; 9 studies included females only. For retrospective studies, the pooled persistence estimates were 74.6% (95% CI: 65.4-82.9) at 12 months, 67.6% (65.2-70.0) at 18 months, and 57.2% (51.8-62.5) at 24 months. For prospective studies, the pooled estimate of 12-month persistence was 89.0% (95% CI: 84.6-92.7). In the subgroup analysis, European studies had higher pooled 12-month persistence estimates compared with North American studies (retrospective: 78.6% vs. 68.9%; prospective: 91.5% vs. 85.3%). CONCLUSIONS To our knowledge, this is the first systematic review and meta-analysis of persistence with denosumab in patients with osteoporosis. We identified a growing body of evidence, both prospective and retrospective, suggesting persistence to denosumab is higher than previously reported for other OP therapies