Objectives This study aimed to assess the economic burden of subsequent fracture in osteoporosis patients with incident fracture. Methods The authors conducted a retrospective cohort analysis of the South Korean national health insurance claims data. Study subjects included osteoporosis patients aged >= 50 with incident fracture (July 1, 2014-June 30, 2015). Fracture-related 1-year healthcare cost was evaluated after incident fracture for patients with and without subsequent fracture, defined as a fracture occurring within 2 years from incident fracture at a different site or at the same site after 6-months washout period. Per-patient-per-month (PPPM) cost was calculated by dividing each patient's cumulative healthcare cost until subsequent fracture with time-to-subsequent-fracture. For the patients without subsequent fracture, PPPM cost equaled 1-year monthly cost. A generalized linear model (GLM) was used to estimate the ratio of increase in healthcare cost to assess the economic impact of subsequent fracture. Results A total of 73,717 osteoporosis patients with incident fracture were identified, consisting of 52.1% vertebral, 1.9% hip, and 46.0% non-vertebral-non-hip fractures. Subsequent fracture occurred in 17.9% of patients with average time-to-subsequent-fracture of 256 days. Patients with subsequent fracture had significantly higher 1-year healthcare cost after incident fracture than those without subsequent fracture ($4,307 vs $1,721) and the difference was greater in PPPM cost ($930 vs $141). GLM analysis showed that having subsequent fracture increased both 1-year healthcare cost and PPPM cost by 1.91-fold (95% CI = 1.87-1.95) and 6.14-fold (95% CI = 5.99-6.28), respectively. Conclusions Subsequent fracture imposes a substantial burden on osteoporosis patients and, therefore, more efforts are needed for preventing subsequent fracture among osteoporosis patients.