This study evaluated the association between atrial fibrillation (AF) and 30-day clinical outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Between January 2005 and October 2009, 783 consecutive patients with acute STEMI undergoing primary PCI were enrolled. Of these patients, 85 (10.9%) with AF during admission were categorized into group 1, while the remaining 698 (89.1%) with sinus rhythm during admission served as group 2. The results demonstrated that the incidence of advanced Killip score (defined as ≥ score 3) and advanced congestive heart failure (defined as ≥ NYHA class 3) were significantly higher, whereas the left ventricular ejection fraction (LVEF) was notably lower in group 1 than in group 2 (all P < 0.003). Additionally, the normal blood flow in the infarct-related artery was notably lower in group 1 than in group 2 (P = 0.003). Moreover, the incidences of new-onset stroke and 30-day mortality were remarkably higher in group 1 than in group 2 (all P < 0.003). Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was markedly lower in AF patients than in those with sinus rhythm. However, multivariate stepwise Cox regression analysis demonstrated that the advanced Killip score and low LVEF were significantly and independently predictive of 30-day mortality (all P < 0.004). In conclusion, AF was significantly associated with 30-day mortality.