Purpose of Review: In this review, we present the application of pragmatic clinical trials for evaluating interventions in osteoporosis, and we discuss methodological considerations for designing and conducting a pragmatic clinical trial compared with a classical randomized clinical trial. Recent Findings: Pragmatic clinical trials are a popular study design testing effectiveness of health interventions and are intended to address the limitations associated with traditional explanatory randomized clinical trials testing efficacy of interventions. To date, only few pragmatic clinical trials have been conducted in osteoporosis. Summary: Pragmatic clinical trials are conducted under routine clinical practice setting and are intended to inform policy makers and clinical decisions. Osteoporosis is a chronic disease well-suited to this particular study design given the existence of a clear and specific natural endpoint, namely fracture occurrence, and the availability of several treatments to prevent fractures.