Objective(s): To test if acute kidney injury (AKI) is preventable in patients in the neonatal intensive care unit and if infants at high-risk of nephrotoxic medication-induced AKI can be identified using a systematic surveillance program previously used in the pediatric non-intensive care unit setting. Study design: Quality improvement project that occurred between March 2015 and September 2017 in a single center, level IV neonatal intensive care unit. Infants were screened for high-risk nephrotoxic medication exposure (≥3 nephrotoxic medication within 24 hours or ≥4 calendar days of an intravenous [IV] aminoglycoside). If infants met criteria, a daily serum creatinine (SCr) was obtained until 2 days after end of exposure or end of AKI, whichever occurred last. The study was divided into 3 eras: pre-Nephrotoxic Injury Negated by Just-in-time Action (NINJA), initiation, and sustainability. Differences for 5 metrics across 3 eras were compared: SCr surveillance, high nephrotoxic medication exposure rate (per 1000 patient-days), AKI rate (per 1000 patient-days), nephrotoxin-AKI percentage, and AKI intensity (number of AKI days per 100 susceptible patient-days). Results: Comparing the initiation with sustainability era, there was a reduction in high nephrotoxic medication exposures from 16.4 to 9.6 per 1000 patient-days (P = .03), reduction in percentage of nephrotoxic medication-AKI from 30.9% to 11.0% (P < .001), and reduction in AKI intensity from 9.1 to 2.9 per 100 susceptible patient-days (P < .001) while maintaining a high SCr surveillance rate. This prevented 100 AKI episodes during the 18-month sustainability era. Conclusion(s): A systematic surveillance program to identify high-risk infants can prevent nephrotoxic-induced AKI and has the potential to prevent short and long-term consequences of AKI in critically ill infants.