Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/ tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.