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Studies evaluating the outcomes of an extended-infusion (EI) piperacillin-tazobactam dosing strategy in specific cohorts of critically ill patients are lacking. A retrospective, pre-implementation and post-implementation study of 148 critically ill patients was conducted to compare EI and traditional infusion piperacillin-tazobactam. In this retrospective study, the EI piperacillin-tazobactam dosing strategy was associated with improved 30-day mortality. EI piperacillin-tazobactam may be an effective alternative to TI of piperacillin-tazobactam among critically ill patients treated for suspected gram-negative infections.