The purpose of this study was to evaluate the protective effect of oral hydration volume to weight ratio (OHV/W) on contrast-induced acute kidney injury (CI-AKI) among patients with ST-elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI).A total of 754 patients with STEMI undergoing PCI were selected. Each patient was encouraged to drink as much water as possible 24 h after PCI. Total volume intake was recorded for all patients. The ratio of OHV/W was calculated. The occurrence of CI-AKI was defined as ≥0.5 mg/dL absolute or ≥25% relative increase in serum creatinine within 48-72 h following PCI. Logistic regression analysis and generalized additive model were performed to evaluate the relationship between OHV/W and CI-AKI.There was a nonlinear relationship between OHV/W and CI-AKI with an inflection point of 15.69 mL/kg. On the right side of the inflection point (OHV/W ≥15.69 mL/kg), a negative relationship was detected between OHV/W and CI-AKI (HR = 0.90, 95% CI: 0.82∼0.98, p = 0.0126). However, no relationship was observed between OHV/W and CI-AKI on the left of inflection point (HR = 1.19, 95% CI: 0.95∼1.49, p = 0.1302). Subgroup analysis showed that significant interactions were observed only for gender difference (p for interaction = 0.0155), male patients had a significantly lower risk of CI-AKI (HR = 0.84, 95% CI: 0.75∼0.93, p = 0.0012).OHV/W ≥15.6 mL/kg for 24 h post-procedure may be an effective preventive strategy of CI-AKI. In addition, male patients may particularly benefit from OHV to prevent CI-AKI.© 2021 The Author(s). Published by S. Karger AG, Basel.