Abstract Disclosure: R.H. Lee: None. Y. Wang: Employee; Self; Radius Health, Inc. S.A. Williams: Employee; Self; Star Biopharma, LLC. N. Pyrih: Employee; Self; Cobbs Creek Healthcare. B.H. Mitlak: Employee; Self; Radius Health, Inc. J.R. Curtis: Consulting Fee; Self; Amgen Inc, Eli Lilly & Company, Radius Health, Inc, UCB. Grant Recipient; Self; Amgen Inc, Eli Lilly & Company, Radius Health, Inc, UCB. Background: Management of osteoporosis (OP)-related fractures in men is suboptimal. Real-world evidence suggests that, after men sustain a first fracture, they experience a higher risk for subsequent fracture and greater mortality compared to women. There is limited knowledge regarding absolute risk and predictors of second fractures in men and fracture risk assessment tools may be less accurate in men (Vilaca et al 2022). The objective of this study was to develop a model to identify risk factors for a second fracture in men in the year following an initial fracture. Methods: Anonymized patient-level medical and pharmacy claims data from Symphony Health PatientSource® were used. The study criteria included males ≥40 years with a case-qualifying OP-related fracture between January 1, 2017 to May 31, 2021 based on a claims-based validated algorithm (Wright et al 2019). Logistic regression models with a binary outcome of a second fracture versus no second fracture within one year of index fracture were created to predict second fracture occurrence. The study built upon a previous model (Williams et al 2021) developed for OP-related fractures for both men and women incorporating additional variables relevant to men based on the current literature. A separate model to identify risk factors for a secondary nonvertebral fracture (NVF) in men was also developed. Results: Of 956,828 men identified with an index fracture (677,047 commercial; 279,781 Medicare Advantage), 13% (126,106) experienced a second fracture within 1 year following the index fracture. More than two thirds of secondary fractures were NVFs. Multivariable logistic regression showed that patients with an index fracture at the spine (OR [95% CI] 1.71 [1.68, 1.74]) or hip (OR [95% CI] 1.79 [1.75, 1.82]) were the most likely to have a second fracture within a year of index fracture. An index clinical spine fracture was not associated with an increased risk of secondary NVFs. Nonfracture spinal cord injury was included among the predictors with the greatest magnitude of estimate for NVF (OR [95% CI] 1.21 [1.08, 1.36]). In addition to fracture history, advanced age, history of falls, use of medications that increase fall risk, OP diagnosis, treatment with OP medication, low body weight, and excessive alcohol use were significant and the numerically largest predictors for a second fracture. Type 2 diabetes, but not GLP-1 use, also increased risk of secondary fracture. Variables negatively associated with future fractures included treatment history with alpha blockers (beta blockers in the Medicare cohort) and diuretics. Conclusion: Predictors of fracture in men were overall consistent with the literature (and risk factors identified in the FRAX risk calculator). Regardless of gender, recent fracture is always the highest risk factor for a secondary fracture. Presentation: 6/3/2024