ObjectiveDeprescribing opportunities may differ across health care systems, nursing home settings, and prescribing cultures. The objective of this study was to compare the prevalence of STOPPFrail medications according to frailty status among residents of nursing homes in Australia, China, Japan, and Spain. DesignSecondary cross-sectional analyses of data from 4 cohort studies. Setting and ParticipantsA total of 1142 residents in 31 nursing homes. MethodsMedication data were extracted from resident records. Frailty was assessed using the FRAIL-NH scale (non-frail 0–2; frail 3–6; most-frail 7–14). Chi-square tests and prevalence ratios (PRs) were used to compare STOPPFrail medication use across cohorts. ResultsIn total, 84.7% of non-frail, 95.6% of frail, and 90.6% of most-frail residents received ≥1 STOPPFrail medication. Overall, the most prevalent STOPPFrail medications were antihypertensives (53.0% in China to 73.3% in Australia, P < .001), vitamin D (nil in China to 52.7% in Australia, P < .001), lipid-lowering therapies (11.1% in Japan to 38.9% in Australia, P < .001), aspirin (13.5% in Japan to 26.2% in China, P < .001), proton pump inhibitors (2.1% in Japan to 32.0% in Australia, P < .001), and antidiabetic medications (12.3% in Japan to 23.5% in China, P = .010). Overall use of antihypertensives (PR, 1.15; 95% CI, 1.06–1.25), lipid-lowering therapies (PR, 1.78; 95% CI, 1.45–2.18), aspirin (PR, 1.31; 95% CI, 1.04–1.64), and antidiabetic medications (PR, 1.31; 95% CI, 1.00–1.72) were more prevalent among non-frail and frail residents compared with most-frail residents. Antihypertensive use was more prevalent with increasing frailty in China and Japan, but less prevalent with increasing frailty in Australia. Antidiabetic medication use was less prevalent with increasing frailty in China and Spain but was consistent across frailty groups in Australia and Japan. Conclusions and ImplicationsThere were overall and frailty-specific variations in prevalence of different STOPPFrail medications across cohorts. This may reflect differences in prescribing cultures, application of clinical practice guidelines in the nursing home setting, and clinician or resident attitudes toward deprescribing.