Potential effects of supratherapeutic doses of intravenous (IV) ceftazidime–avibactam and ceftaroline fosamil–avibactam on cardiac repolarization were assessed in a thorough QT/QTc study. This was a double-blind, randomized, placebo-controlled, four-period crossover Phase I study (NCT01290900) in healthy males (n = 51). Subjects received, in randomized order and separated by ≥3 days washout: single doses of IV ceftaroline fosamil 1,500 mg with avibactam 2,000 mg; IV ceftazidime 3,000 mg with avibactam 2,000 mg; oral moxifloxacin 400 mg (open-label positive control); and IV placebo (saline). Least square mean and two-sided 90% confidence intervals (CI) for change from baseline in Fridericia-corrected QT interval (ΔQTcF) for active treatments versus placebo were estimated at 10 time points over 24 hours. The upper bound of the two-sided 90% CI for placebo-corrected ΔQTcF did not exceed 10 milliseconds at any time point over 24 hours for ceftaroline fosamil–avibactam or ceftazidime–avibactam. The lower bound of the two-sided 90% CI for the difference between moxifloxacin and placebo in ΔQTcF over 1–4 hours was >5 milliseconds, confirming assay sensitivity. Pharmacokinetics results confirmed achievement of supratherapeutic plasma concentrations. No safety concerns were raised. In conclusion, supratherapeutic doses of ceftaroline fosamil–avibactam or ceftazidime–avibactam were not associated with QT/QTc prolongation in this study population.