Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014–2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure:​ none, 1–90 days, and >90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for >90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82;​ 95% confidence interval [CI] 0.68–1.00) overall. Results were similar in frail (HR = 0.85;​ 95% CI 0.65–1.12) and non-frail (HR = 0.80;​ 95% CI 0.61–1.04) patients but not significant. In conclusion, osteoporosis treatment >90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy.