Introduction: Despite the efficacy of bisphosphonates to reduce fractures in high risk populations, bisphosphonate adherence among chronic glucocorticoid users has received limited attention. Moreover, perceived differences in GI tolerability may lead physicians to preferentially prescribe particular bisphosphonates. Methods: Among chronic glucocorticoid users (>60 days of therapy) enrolled in managed care, we identified individuals initiating therapy with alendronate or risedronate during 2001-2004. Multivariable logistic regression and proportional hazards models were used to examine factors associated with channeling patients to risedronate (versus alendronate) and with discontinuation (>3-month gap without refill). The Medication Possession Ratio (MPR) was calculated as the filled days of medication divided by the interval of time between prescriptions. Results: Of 1,158 glucocorticoid users initiating bisphosphonate therapy, demographic characteristics of alendronate users (n=754) and risedronate users (n=404) were similar for age (mean 53 years) and gender (approximately 80% female). Past history of a GI symptom or event was associated with risedronate receipt (OR=2.24, 95% CI 1.15-4.35). After multivariable adjustment, rates of discontinuation (mean time to discontinuation approximately 18 months) and adherence (mean MPR=73%) were similar between users of the two bisphosphonates. Younger age, greater medical comorbidity, and lack of BMD testing were significantly associated with discontinuation. Conclusions: Overall persistence rates were suboptimal for bisphosphonate use among chronic glucocorticoids users and did not differ significantly by drug. Newer strategies to promote long-term adherence are needed to improve osteoporosis therapeutic effectiveness. © International Osteoporosis Foundation and National Osteoporosis Foundation 2006.