OBJECTIVE: To compare treatment patterns, specifically persistence and compliance, among postmenopausal osteoporotic women treated with daily or weekly bisphosphonates. METHODS: Data were obtained from a US managed care database. The study cohort included women with an osteoporosis diagnosis (ICD-9 code 733.0) followed by a prescription for alendronate 10mg (daily) or 70mg (weekly), risedronate 5mg (daily) or 35mg (weekly) between 01/2001 and 06/2002. The first prescription for one of these medications was considered the index prescription. Non-persistence was defined as a >30 days gap between two subsequent prescriptions. Compliance was measured using the medication possession ratio (MPR), with analyses conducted using both continuous and categorical definitions. Outcomes were compared between daily and weekly regimens. RESULTS: Of the 2905 new users identified based on a 6-month run-in, 31% had an index prescription for a daily regimen, 69% for a weekly regimen. After six months, 46.7% of women on the weekly regimen and 41.9% on the daily regimen persisted with their therapies. At 12 months, the percentages were 27.7% and 18.9%. Longer persistence was thus observed for once-weekly users (median: 146 vs 120 days), but the differences were not significant. At 12 months, weekly users had a significantly higher MPR than daily users (53.7% vs 46.9%, P=0.0022). Similarly, the proportion of highly compliant patients (≥80%) was 23% for the daily versus 32% for the weekly regimen (P=0.0025). A larger proportion of patients starting on a weekly regimen remained on the same treatment over time (98% vs. 42% for those still treated at 12 months). An average of 1.15 switches per patient was observed. CONCLUSIONS: Although higher rates of compliance are observed for the weekly compared to the daily regimen, compliance and persistence rates for both regimens are suboptimal, and the social and economic implications of such behavior are known to be substantial.