OBJECTIVES: To assess patient adherence with bisphosphonates at 6 months of therapy utilizing an integrated administrative, medical and pharmacy claims database. METHODS: A retrospective cohort study was conducted among 128,362 women, 45 years of age and older, with a new (index) prescription for risedronate (35mg/week) or alendronate (35mg/week or 70mg/week) between May 1, 2002, and December 31, 2003. All eligible patients were required to be continuously enrolled for the six months preceding and the 12 months following the index date and to have filled at least 2 continuous bisphosphonate prescriptions, as defined below. The six-month history was used to assess baseline clinical characteristics, including fracture history, gastrointestinal conditions, hospitalizations, and glucocorticoid use. Adherence with therapy was then assessed for the first 6 months of bisphosphonate treatment. Patient adherence was defined as continuous refilling of the weekly bisphosphonate treatment with no gaps exceeding 90 days during the follow-up period. RESULTS: The average bisphosphonate user in this study was aged 64 years; 78% initiated with alendronate and 22% with risedronate. Almost 4% had a history of fragility fractures (vertebral and/or non-vertebral) and 18% used oral glucocorticoids during the study period. At 6 months, 71% of bisphosphonate patients were adherent with therapy. An additional 22% discontinued, and subsequently resumed treatment after a mean treatment gap of 164 days. The following patient characteristics were correlated with a higher likelihood of therapy discontinuation: younger age, GI event after the index date, oral glucocorticoid use, and history of GI events, hospitalization, or fracture. CONCLUSIONS: This study demonstrates that seven in ten new bisphosphonate users remained on therapy at six months after treatment initiation. An additional two in ten patients resumed therapy after a mean treatment gap of five months. Overall, the majority of patients who initiated bisphosphonates were adherent after the first six months of treatment.