Objectives: 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). Methods: 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. Results: 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). Conclusion: 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.