Background:Red cell distribution width (RDW) is known to be associated with anemia and mortality in cardiovascular diseases, while anemia itself is related to increased mortality. RDW may also be related to cytokine activation. We investigated the potential of RDW to predict anemia-adjusted mortality in patients with adult congenital heart disease (ACHD) and we evaluated the relationships among RDW, anemia, and interleukin-6 (IL-6).Methods and Results:This was a single-center, retrospective cohort study. Blood RDW and IL-6 levels were measured in 144 patients with ACHD (median age [interquartile range (IQR)], 28 [22–36] years), 84% in New York Heart Association class I/II. During a mean 4.8-year follow-up, 21 (15%) patients died of cardiovascular causes. Elevated RDW (>15.0%) correlated significantly with mortality risk in a univariate analysis (RDW hazard ratio [HR]: 1.570; 95% confidence interval [CI]: 1.208–2.040 per 1 standard deviation increase; P=0.001). Elevated RDW levels correlated significantly with increased anemia-adjusted mortality (adjusted RDW HR: 1.912; 95% CI: 1.369–2.670; P<0.001). The high RDW group had significantly elevated serum IL-6 levels (RDW >15%, median [IQR], 3.7 [0.9–13.9] pg/ml vs. RDW ≤15%, 1.4 [0.8–2.5 pg/ml]; P=0.001), as did patients with anemia (anemia, 1.9 [0.9–5.2] pg/ml vs. no anemia, 1.4 [0.8–2.5 pg/ml]; P=0.021).Conclusions:Elevation of RDW may be related with increased IL-6 and anemia-adjusted cardiovascular mortality in patients with ACHD. (Circ J 2015; 79: 1100–1106)