Abstract Objective To investigate symptomatic and preventive medication use according to age and frailty in Australian and Japanese nursing homes (NHs). Methods Secondary cross-sectional analyses of two prospective cohort studies involving 12 Australian NHs and four Japanese NHs. Frailty was measured using the FRAIL-NH scale (non-frail 0–2; frail 3–6; most-frail 7–14). Regular medications were classified as symptomatic or preventive based on published lists and expert consensus. Descriptive statistics were used to compare the prevalence and ratio of symptomatic to preventive medications. Results Overall, 550 Australian residents (87.7 ± 7.3 years; 73.3% females) and 333 Japanese residents (86.5 ± 7.0 years; 73.3% females) were included. Australian residents used a higher mean number of medications than Japanese residents (9.8 ± 4.0 vs 7.7 ± 3.7, p < 0.0001). Australian residents used more preventive than symptomatic medications (5.5 ± 2.5 vs 4.3 ± 2.6, p < 0.0001), while Japanese residents used more symptomatic than preventive medications (4.7 ± 2.6 vs 3.0 ± 2.2, p < 0.0001). In Australia, symptomatic medications were more prevalent with increasing frailty (non-frail 3.4 ± 2.6; frail 4.0 ± 2.6; most-frail 4.8 ± 2.6, p < 0.0001) but less prevalent with age (< 80 years 5.0 ± 2.9; 80–89 years 4.4 ± 2.6; ≥ 90 years 3.9 ± 2.5, p = 0.0042); while preventive medications remained similar across age and frailty groups. In Japan, there was no significant difference in the mean number of symptomatic and preventive medications irrespective of age and frailty. Conclusions The ratio of symptomatic to preventive medications was higher with increasing frailty but lower with age in Australia; whereas in Japan, the ratio remained consistent across age and frailty groups. Preventive medications remained prevalent in most-frail residents in both cohorts, albeit at lower levels in Japan.