Summary: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among Medicare Advantage Prescription Drug (MAPD) plan members. Treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs. Overall adherence remained low. Introduction: We examined the association between osteoporosis treatment change and adherence, incident fractures, and healthcare costs among MAPD plan members in a large US health plan. Methods: We conducted a retrospective cohort study of MAPD plan members aged ≥50 years newly initiated on an osteoporosis medication between 1 January 2006 and 31 December 2008. Members were identified as having or not having an osteoporosis treatment change within 12 months after initiating osteoporosis medication. Logistic regression analyses and difference-in-difference (DID) generalized linear models were used to investigate the association between osteoporosis treatment change and (1) adherence to treatment, (2) incident fracture, and (3) healthcare costs at 12 and 24 months follow-up. Results: Of the 33,823 members newly initiated on osteoporosis treatment, 3,573 (10.6 %) changed osteoporosis treatment within 12 months. After controlling for covariates, osteoporosis treatment change was associated with significantly higher odds of being adherent (medication possession ratio [MPR] ≥ 0.8) at 12 months (odds ratio [OR] = 1.18) and 24 months (OR = 1.13) follow-up. However, overall adherence remained low (MPR = 0.59 and 0.51 for the change cohort and MPR = 0.51 and 0.44 for the no-change cohort at 12 and 24 months, respectively). Osteoporosis treatment change was not significantly associated with incident fracture (OR = 1.00 at 12 months and OR = 0.98 at 24 months) or total direct healthcare costs (p > 0.4) in the DID analysis, but was associated with higher pharmacy costs (p < 0.004). Conclusions: Osteoporosis treatment change was associated with a small but significant increase in adherence, but was not associated with incident fracture or total healthcare costs in the MAPD plan population. Overall adherence to therapy remained low. © 2012 International Osteoporosis Foundation and National Osteoporosis Foundation.