Serum creatinine is the most commonly used marker to diagnose acute kidney injury. Studies exploring creatinine patterns in the single-ventricle population are scarce. We studied serum creatinine up to 5 postoperative days after the stage 1 operation and assessed its relationship with outcomes. Neonates who underwent a first-stage single-ventricle operation (Norwood or a Damus-Kaye-Stansel) between 2005 and 2017 were retrospectively analyzed. Peak percentage creatinine change (PPCC) was defined as the difference between the baseline (preoperative) and the peak postoperative level (within 5 postoperative days), expressed as a percentage of the baseline level. Among 187 neonates included, the median PPCC was 38.7% (interquartile range, 14.1%-73.1%), and in-hospital mortality was 17% (31 of 187). A controlled analysis showed that for every 10-minute increase in cardiopulmonary bypass duration (CPB), the PPCC increased by 1.8% (95% confidence interval [CI], 0.7%-2.9%; P= .002). Risk of in-hospital death increased log-linearly with PPCC. The adjusted odds ratios for death in the hospital associated with a 50%, 100%, and 200%, increase in peak percentage creatinine change were 1.85 (95% CI, 1.23-2.78), 3.41 (95% CI, 1.15-7.72), and 11.66 (95% CI, 2.28-59.63), respectively. In-hospital death was also associated with CPB duration (adjusted odds ratio, 1.13 per 10-minute increase; 95% CI, 1.05-1.22; P= .001). Increase in CPB duration has a strong linear association with increase in PPCC after stage 1 single-ventricle reconstruction. Increase in PPCC and CPB duration has a strong linear association with hospital mortality. It is important to identify therapies that minimize complications associated with prolonged CPB duration in high-risk populations.