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This randomized crossover study in healthy participants assessed pharmacokinetic interactions between telavancin, aztreonam, and piperacillin/tazobactam. Part 1: 11 participants received telavancin 10 mg/kg, aztreonam 2 g, or a combination of telavancin 10 mg/kg + aztreonam 2 g intravenously on 3 separate days. Part 2: 12 participants received telavancin 10 mg/kg, piperacillin/tazobactam 4.5 g, or a combination of telavancin 10 mg/kg + piperacillin/tazobactam 4.5 g intravenously on 3 separate days. Blood and urine drug concentrations were measured up to 48 hours posttreatment. Drug interactions were assessed by equivalence analysis of noncompartmental pharmacokinetic parameters, focusing on area under plasma concentration-time curves (AUC), log transformed; if the antilog of the 90% confidence intervals (CIs) for the mean log AUC difference was within equivalence bounds (0.70, 1.43), the effect of coadministration on the pharmacokinetics of the respective drug was deemed not clinically significant. Plasma concentration-time curves for all treatment pairs were nearly superimposable with comparable values for pharmacokinetic parameter estimates. In equivalence analyses, 90% CI for the mean difference in log AUC in each comparison fell within the predefined clinical equivalence limits and bioequivalence limits (0.80, 1.25). Administration of aztreonam or piperacillin/tazobactam with telavancin had no clinically significant effect on the pharmacokinetic disposition of any of these drugs.