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ABSTRACT Atypical femoral fractures (AFFs) have been reported in patients taking bisphosphonates (BPs) for osteoporosis therapy but also in patients with no exposure to these drugs. In contrast, less is known about the incidence of AFFs in patients taking denosumab. This registry‐based cohort study analyzed the incidence of AFFs in patients with suspected or confirmed osteoporosis who were included in the osteoporosis register of the Swiss Society of Rheumatology between January 2015 and September 2019. Statistical analyses included incidence rates, rate ratios, and hazard ratios for AFFs, and considered sequential therapies and drug holidays as time‐dependent covariates. Among the 9956 subjects in the cohort, 53 had subtrochanteric or femoral shaft fractures. Ten fractures occurred under BP or denosumab treatment and two under teriparatide therapy. Five fractures were classified as AFFs based on the revised American Society of Bone and Mineral Research case definition of AFFs from 2014. Three AFFs occurred in women being treated with denosumab at the time of diagnosis, all with prior BP use (10, 7, and 1 years, respectively). One AFF developed in a woman receiving ibandronate and one arose in a woman receiving glucocorticoids rather than antiresorptive therapy. The incidence of AFFs per 10,000 observed patient‐years was 7.1 in patients receiving denosumab and 0.9 in patients with BP‐associated AFFs, yielding a rate ratio of 7.9 (95% confidence interval [CI] 0.63–413), p = 0.073. The risk of AFFs was not significantly higher in patients receiving denosumab therapy compared with BP therapy (hazard ratio = 7.07, 95% CI 0.74–68.01, p = 0.090). We conclude that the risk of AFFs is low in patients taking BPs, denosumab, or both sequentially. All three patients with AFFs under denosumab therapy had undergone prior BP therapy. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.