Aim To investigate the effect of continuous intravenous injection of nicorandil on the incidence of contrast-induced acute kidney injury (CI-AKI) in patients with acute ST-segment elevation myocardial infarction(STEMI) undergoing primary percutaneous coronary intervention(PPCI). Methods A total of 397 patients with STEMI undergoing PPCI were enrolled in this prospective randomized controlled trial. Patients were randomly assigned into two groups:the nicorandil group(n=199)and the control group(n=198). The primary outcome was the incidence of CI-AKI, the secondary outcomes included the major adverse cardiovascular events (MACE) during hospitalization and the need of renal replacement therapy. Results The average of myocardial ischemia was (6.1±2.1) hours. No significant difference was observed in Mehran score and other baseline characteristics between groups (P>0.05). The median duration of blood sampling time after operation was 28.5(25.3,9.6)hours. As a result, there were 53(13.4%) out of 397 patients suffered from CI-AKI, 17(8.5%) in the nicorandil group and 36(18.2%) in the control group, respectively (P<0.05). In the multivariate Logistic regression model, nicorandil acted as an independent protective factor of CI-AKI(OR=0.38, 95% CI 0.20～0.72, P=0.003). Whereas, the volume of CM(OR=1.03, 95% CI 1.01～1.04, P<0.001)was an independent risk factor for CI-AKI. The incidence of angina within 24 hours post PPCIin control group was higher than that in nicorandil group (P<0.05). There was no significant difference in MACE, and renal replacement therapy between the two groups (P>0.05). Conclusion Intravenous injection of nicorandil perioperatively can reduce the incidence of CI-AKI in STEMI patients undergoing PPCI, but does not improve the short-term prognosis.