© 2017 American Pharmacists Association® Objectives As many as one-half of patients recommended for osteoporosis pharmacotherapy do not take their medications. To identify intervention targets, we examined patient characteristics associated with nonadherence to recommended pharmacotherapy and their reasons for nonadherence. Methods Data come from the Patient Activation after DXA Result Notification (PAADRN) study, a randomized controlled trial of 7749 patients aged 50 years or older presenting for dual-energy X-ray absorptiometry (DXA) at 3 health centers in the United States. We focused on the 790 patients who reported receiving a recommendation for new pharmacotherapy at baseline. Using Pearson chi-squared tests for categorical variables, 2-sample t tests for continuous variables, and multivariable multinomial logistic regression, we compared those who reported starting the recommended medication (adherers) with temporary nonadherers and nonadherers on demographics, health habits, DXA impression, 10-year probability of fracture using the assessment tool, and osteoporosis knowledge, and we examined their stated reasons for nonadherence. Results Mean age was 66.8 years (SD = 8.9); 87.2% were women, and 84.2% were white. One-fourth of patients (24.8%) reported that they did not start their recommended pharmacotherapy. In the unadjusted analyses, the only factor significantly associated with nonadherence was osteoporosis knowledge, with those having better knowledge being less likely to take their medications (P < 0.05). The most common reasons for nonadherence were fear of adverse effects (53.3%), a dislike of taking medicine (25.3%), and the belief that the medication would not help their condition (16.7%). Conclusion One in 4 patients recommended for osteoporosis pharmacotherapy declined treatment because they feared potential adverse effects, did not like taking medicine, or believed that the medication would not help their condition. Improved patient counseling on the potential adverse effects of osteoporosis treatment and the risk-benefit ratio for these medications may increase adherence.