Abstract Aims Because an increased risk of amputation with canagliflozin was reported in the CANVAS trials, there has been a concern about the safety of sodium–glucose cotransporter 2 inhibitors in patients with peripheral artery disease (PAD) who are at higher risk of amputation. Methods and results A patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the efficacy and safety of dapagliflozin in patients with heart failure (HF) with reduced, mildly reduced/preserved ejection fraction, respectively, was conducted. In both trials, the primary outcome was the composite of worsening HF or cardiovascular death, and amputation was a prespecified safety outcome. Peripheral artery disease history was available for 11 005 of the total 11 007 patients. Peripheral artery disease was reported in 809 of the 11 005 patients (7.4%). Median follow-up was 22 months (interquartile range 17–30). The rate of the primary outcome (per 100 person-years) was higher in PAD patients than that in non-PAD patients: 15.1 [95% confidence interval (CI) 13.1–17.3) vs. 10.6 (10.2–11.1]; adjusted hazard ratio 1.23 (95% CI 1.06–1.43). The benefit of dapagliflozin on the primary outcome was consistent in patients with [hazard ratio 0.71 (95% CI 0.54–0.94)] and without PAD [0.80 (95% CI 0.73–0.88)] (Pinteraction = 0.39). Amputations, while more frequent in PAD patients, were not more common with dapagliflozin, compared with placebo, irrespective of PAD status (PAD, placebo 4.2% vs. dapagliflozin 3.7%; no PAD, placebo 0.4% vs. dapagliflozin 0.4%) (Pinteraction = 1.00). Infection rather than ischaemia was the main trigger for amputation, even in patients with PAD. Conclusion The risk of worsening HF or cardiovascular death was higher in patients with PAD, as was the risk of amputation. The benefits of dapagliflozin were consistent in patients with and without PAD, and dapagliflozin did not increase the risk of amputation.