The purpose of this study is to compare the incidence of acute renal injury (ARI) in patients on intermittent infusion to extended infusion piperacillin/tazobactam. Data was collected for the intermittent infusion group from November 2010 to December 2010 until 100 patients were enrolled. The data was then compared to 100 patients in the extended infusion group from November 2011 to December 2011. Patients who received at least three consecutive doses of piperacillin/tazobactam and were inpatient for at least 48 hours were included. Patients were excluded for any of the following: baseline serum creatinine (SCr) ≥4 mg/dL, age less than 18 years old, pregnancy, penicillin allergy, or concurrent use with any cephalosporin or penicillin. The primary endpoint was the incidence of ARI, defined as a SCr two times the baseline or 0.5 mg/dL increase within 24 hours. The secondary endpoint was patient length of stay, measured as actual inpatient days. Eleven patients in the intermittent infusion group and nine patients in the extended infusion group developed ARI (11% vs. 9%, p = 0.637). The length of stay between the intermittent and extended infusion groups was 19 days vs. 14 days, respectively (p = 0.083). The incidence of ARI in patients on piperacillin/tazobactam was similar between the intermittent and extended infusion groups. Larger studies should be considered to confirm that the incidence of ARI associated with piperacillin/tazobactam is not infusion-related.