OBJECTIVES: To compare medication adherence rates for once weekly (QW) versus once daily (QD) dosing regimens in patients with osteoporosis. METHODS: A systematic literature review was conducted to identify articles published in English language journals that evaluated the rate of adherence to medications in patients with chronic disease. Relevant studies were identified using PubMed, EMBASE, and the Cochrane Library databases with a search window from January 2002 through August 2013. Twenty-two observational studies reporting adherence were identified by two independent reviewers. Of these publications, 7 reported complete information on relevant endpoints of studies in patients with osteoporosis. Meta-analyses examined 1) mean difference (MD) in adherence (defined using average medication possession ratio [MPR]) between QW and QD dosing groups and 2) odds ratio for adherence (defined using a cut-off of MPR ≥80%) for QW versus QD dosing. Heterogeneity was assessed using Ivalues and meta-analyses utilized both fixed and random effects models. RESULTS: The random effects meta-analysis revealed a significantly greater MPR with QW compared to QD dosing (pooled MD=12.29% [95% confidence interval (CI) 10.76%-13.82%]; n=9 [data reported in 7 publications]). Due to the high level of heterogeneity (I=83.4%), the fixed effects model results are not appropriate to report for the pooled MD. When examining the odds ratio for adherence, both fixed and random effects models provided similar results due to the low level of heterogeneity (I=7.9%; n=5 [data reported in 3 publications]). Using either model, the pooled odds of being adherent (MPR ≥80%) in the QW dosing group was approximately 1.9 times the odds in the QD dosing group (random effects OR=1.90 [95% CI 1.81-2.00]; fixed effects OR=1.92 [95% CI 1.84-1.99]). CONCLUSIONS: In our meta-analysis, QW dosing was associated with higher MPR values and greater odds of adherence compared to QD dosing in patients with osteoporosis.