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To study the influence of anemia on long-term outcomes of patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI).The study included 5668 consecutive unique patients with acute coronary syndrome who underwent PCI at Mayo Clinic from January 1, 2004, through December 31, 2014. The patients were stratified on the basis of the presence (hemoglobin [Hgb] level, <13 g/dL in men and <12 g/dL in women) and severity (moderate to severe Hgb level, <11 g/dL in men and women) of pre-PCI anemia and compared with patients without anemia. The primary outcomes were in-hospital and long-term all-cause mortality after balancing baseline comorbidities using the inverse propensity weighting method.Unadjusted all-cause in-hospital mortality (4.6% [84 of 1831] vs 2.0% [75 of 3837]) and 5-year follow-up mortality (44.4%  vs 15.4% ) were higher in patients with anemia than in those without anemia (P<.001 for both). After applying inverse propensity weighting analysis, the all-cause in-hospital mortality (2.0%  vs 2.0% ; P=.85) and 5-year mortality (17.8%  vs 15.4% ; P=.05) were not significantly different between patients with and without anemia; however, there were higher rates of all-cause 5-year mortality in patients with moderate to severe anemia (22.3%  vs 15.4% ; P<.001) compared with patients without anemia. The trend in 5-year mortality was driven by increased noncardiac mortality in patients with anemia (10.2%  vs 7.1% ; P=.04) and moderate to severe anemia (10.4%  vs 7.1% ; P=.006) when compared with nonanemic patients.After accounting for differences in risk profiles of anemic and nonanemic patients, anemia appeared to be an independent risk factor for increased long-term all-cause and noncardiac mortality.