Rationale: Data are suggesting that altered antimicrobial concentrations are likely during extracorporeal membrane oxygenation (ECMO). Objectives: The primary aim of this analysis was to describe the pharmacokinetics of antimicrobials in critically ill adult patients receiving ECMO. Our secondary aim was to determine whether current antimicrobial dosing regimens achieve both effective and safe exposure. Methods: This study was a prospective, open-labelled, pharmacokinetic study in six intensive care units from Australia, New Zealand, South Korea and Switzerland. Serial blood samples were collected over a single dosing interval during ECMO for eleven antimicrobials. Pharmacokinetic parameters were estimated using non-compartmental methods. Adequacy of antimicrobial dosing regimens were evaluated using pre-defined concentration exposures associated with maximal clinical outcomes and minimal toxicity risks. Measurements and Main Results: We included 993 blood samples from 85 patients. The mean age was 44.7 ± 14.4 years and 61.2% were males. Thirty-eight patients (44.7%) were receiving renal replacement therapy (RRT) during first pharmacokinetic sampling. Large variations (coefficient of variation of ≥30%) in antimicrobial concentrations were seen leading to more than five-fold variations in all PK parameters across all study antimicrobials. Overall, 70 (56.5%) concentration profiles achieved the pre-defined target concentration and exposure range. Target attainment rates were not significantly different between modes of ECMO and RRT. Poor target attainment was observed across the most frequently used antimicrobials for ECMO patients, including for oseltamivir (33.3%), piperacillin (44.4%), and vancomycin (27.3%). Conclusion: Antimicrobial pharmacokinetics were highly-variable in critically ill patients receiving ECMO leading to poor target attainment rates.