OBJECTIVES: There is limited evidence regarding the role of anticholinergic medications in falls/fractures among the elderly. This study examined the risk of fractures associated with anticholinergic use in elderly nursing home residents with depression. METHODS: A population-based nested case control study was conducted using 2007-2010 Minimum Data Set (MDS)-linked Medicare data from all states. Patients with continuous coverage in Medicare Parts A, B, D and no HMO coverage during the study period or until death were considered. The base cohort included Medicare beneficiaries aged ≥65 years, diagnosed with depression, and no history of falls/fractures in 2007 (Baseline Period). Cases were identified as patients with incident fractures following the baseline period. For each case, 4 age and sex-matched controls were selected using incidence density sampling. The primary outcome was an inpatient or outpatient claim for fractures, between January 1, 2008 and December 31, 2010. Anticholinergic exposure was defined using Anticholinergic Drug Scale (ADS). Prescription of level 2/3 anticholinergic medications 30 days preceding the event date formed the primary exposure. Conditional logistic regression model stratified on matched case-control sets was performed to assess the fracture risk, after controlling for other risk factors of the outcome. RESULTS: The study sample included 43,402 cases of fractures and 173,608 matched controls (Incidence Density 1:4). After adjusting for other risk factors, there was no difference in risk with high-level anticholinergic use compared to non-use (Relative Risk, RR 1.02; 95% Confidence Interval [CI], 1.00-1.04). The findings remained consistent across levels of anticholinergic potency (Level 2, RR 1.01, 95% CI, 0.98-1.06; Level 3, 95% CI, 1.03, 0.99-1.07). CONCLUSIONS: Use of anticholinergic medications was not associated with a higher risk of fractures compared to no use among elderly residents with depression. Given their safety concerns, there is a need to further evaluate other adverse outcomes associated with anticholinergics in the elderly.