Osteoporosis is a chronic disease that requires continuous health care spending for pharmacotherapy and examinations. Osteoporotic fractures are a major economic burden. However, little is known about the economic effects of osteoporosis and osteoporotic fractures in Korea.The purpose of this study was to determine the predictors of osteoporosis-related health care costs and to evaluate the economic effects of fracture prevention through medication adherence among osteoporosis patients.Using the Korea National Health Insurance Claims Database (KNHICD), we identified osteoporosis patients aged 50 years and older from 2011 to 2012. Annual health care costs of osteoporosis were analyzed from the insurer's perspective and compared between patients with fractures and those without fractures. Adherents were defined as patients with a medication possession ratio of ≥80%. A generalized linear model (GLM) was used to estimate the predictors of osteoporosis-related health care costs.The major predictors of osteoporosis-related health care costs were age, medication adherence, and the occurrence of fractures (P < .001). The proportion of fractures among non-adherents was approximately 1.1 times the proportion among adherents. Health care costs per patient with fractures were 3.8 times the costs per patient without fractures. Patients with fractures had higher health care costs due to hospitalization and outpatient costs but lower pharmacy costs than non-adherents. We estimated that about $5 million of health insurance expenses could be saved annually if all non-adherents became adherents.Improved osteoporosis medication adherence can reduce osteoporosis-related health care costs by preventing fractures. Persistent pharmacotherapy for osteoporosis is necessary to prevent osteoporotic fractures and to reduce osteoporosis-related health care costs.