The objective was to assess the impact of baseline anemia on all-cause mortality and whether 12-month dual antiplatelet therapy (DAPT) affects 1-year mortality linked to anemia in patients after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). 4109 enrolled patients divided into three groups based on their pre-procedural hemoglobin (Hb) level: Hb < 100 mg/L represented moderate-severe anemia; 100 mg/L ≤ Hb < 120 mg/L for women and 100 mg/L ≤ Hb < 130 mg/L for men represented mild anemia; Hb ≥ 20 mg/L for women and Hb ≥ 130 mg/L for men represented no anemia. DAPT medications were prescribed when patients were discharged. There were significant differences in 30-day and 1-year mortality between moderate-severe anemia and no anemia patients (HR 8.05, 95% CI 1.46 to 44.33, P = 0.017; HR 3.93, 95% CI 1.11 to 13.98, P = 0.034), and in long-term mortality between anemia and no anemia groups (HR 1.82, 95% CI 1.17 to 2.83, P = 0.008 for mild anemia; HR 3.19,95% CI 1.29 to 7.86, P = 0.012 for moderate-severe anemia). There was not significant interaction between 12-month DAPT and anemia on mortality in anemic patients (P for interaction > 0.05). Anemia shows association with increased all-cause mortality in patients undergoing PCI. Twelve-month DAPT does not show synergy with anemia to increase the risk of all-cause 1-year mortality in anemic patients after PCI.