OBJECTIVE: To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI). DESIGN: Cohort study from fiscal years 2002 to 2007. SETTING: Medical centers. PARTICIPANTS: Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides. INTERVENTION: Thiazide use versus nonuse. MAIN OUTCOME MEASURE: Incident lower extremity fractures. RESULTS: Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95). CONCLUSIONS: Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures.