Contrast-induced nephropathy (CIN) is a common adverse event in the diagnosis and treatment of coronary intervention. The current study investigated the predictive effect of preoperative fibrinogen (FIB) combined with antithrombin III (AT-III) on CIN following percutaneous coronary intervention (PCI). A total of 394 patients who underwent PCI between October 2018 and May 2019 were selected for the present study. Pre-procedural FIB levels and AT-III activity were measured before PCI. CIN was defined as a 0.5 mg/dl or 25% increase in serum creatinine levels 48 to 72 h after exposure to a radiocontrast agent. Patients were classified into CIN and non-CIN groups. CIN occurred in 48 (12.2%) patients. The serum FIB levels were significantly higher in patients who developed CIN compared with those who did not develop CIN. In addition, AT-III levels ≤89.5% were associated with higher rates of CIN. Logistical regression analysis showed that high FIB, and low AT-III and albumin levels were high-risk factors associated with CIN. For FIB, the area under the receiver operating characteristic curve (AUC) for predicting CIN was 0.653. The optimal cutoff value was 3.48 g/l with a sensitivity of 45.8% and a specificity of 79.7% [95% confidence interval (CI): 0.603-0.701; P= 0.0002)]. For AT-III, the AUC was 0.711, and the optimal cutoff value was 89.5%, with a sensitivity of 81.3% and specificity of 58.2% (95% CI: 0.659-0.758; P<0.0001). When combining FIB and AT-III, the AUC was 0.747. The optimal cutoff value was 0.090424, with a diagnostic sensitivity of 93.8% and specificity of 46.6% (95% CI: 0.697-0.792; P<0.0001). The results showed that FIB combined with AT-III resulted in improved predictive accuracy of CIN (FIB vs. AT-III, AUC= 0.653 vs. 0.711, P= 0.292; FIB vs. FIB + AT-III, AUC= 0.653 vs. 0.747, P= 0.012; AT-III vs. FIB + AT-III, AUC=0.711 vs. 0.747, P=0.138). Pre-procedural levels of FIB, AT-III and albumin were independently associated with an increased risk of CIN. Furthermore, the results suggested that the combination of FIB and AT-III was a better predictor of CIN after PCI.