We aimed to investigate whether the prognostic nutritional index (PNI), a combined nutritional-inflammatory score based on serum albumin levels and lymphocyte count, was associated with mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). From September 2011 to November 2014, 309 consecutive patients with STEMI undergoing pPCI were prospectively enrolled. Patients with a combined score of albumin (g/L) + 5 × total lymphocyte count × 109/L ≥ 45 or <45 were assigned a PNI score of 0 or 1, respectively. Of the 309 STEMI patients, 24 (7.74%) died in the hospital, and 15 (4.83%) died during long-term follow-up (median follow-up time, 19.5 [3-36] months). Compared to patients with a PNI of 0, patients with a PNI of 1 had significantly higher in-hospital (14.2% vs. 3.7%; P < 0.001) and long-term follow-up (21.7% vs. 6.9%, P < 0.001) mortality rates. PNI (1/0, HR, 2.414; 95% CI, 1.016 to 5.736; P = 0.046) was a significant independent predictor of mortality in patients with STEMI undergoing pPCI. Moreover, cumulative survival was significantly lower for patients with a PNI of 1 compared to patients with a PNI of 0 (78.3% vs. 93.1%, log-rank P < 0.001). PNI appears useful for the risk stratification of STEMI patients undergoing pPCI.