Objectives To determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between users of first- and second-generation antipsychotics, and whether fracture rates differ between users of haloperidol, risperidone, olanzapine, and quetiapine. Design Time-to-event analyses were conducted in a retrospective cohort using linked Medicaid; Medicare; Minimum Data Set; and Online Survey, Certification, and Reporting data sets. Setting Nursing homes in California, Florida, Missouri, New Jersey, and Pennsylvania. Participants Nursing home residents aged 65. Measurements Fracture outcomes (any fracture; hip fracture) in users of first- and second-generation anti-psychotic and specifically users of haloperidol, risperidone, olanzapine, and quetiapine. Comparisons incorporated propensity scores that included individual- (demographic characteristics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressive behavior) and facility- (nursing home size, ownership factors, staffing levels) level variables. Results Of 8,262 subjects (in 4,131 pairs), 4.3% suffered any fracture during observation, with 1% having a hip fracture during an average follow-up period of 93 +/- 71days (range 1293days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR)=1.39, P=.004) and hip fracture (HR=1.76, P=.02). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose (HR=2.96, P=.008), but no differences in time to fracture were found between first- and second-generation agents or between individual drugs. Conclusion Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ between commonly used antipsychotics.