Length of stay is the primary driver of heart-failure hospitalization costs. Because cancer antigen 125 has been associated with poor morbidity and mortality rates in heart failure, we investigated the relationship between admission cancer antigen 125 levels and lengths of stay in heart-failure patients. A total of 267 consecutive patients (184 men, 83 women) with acute decompensated heart failure were evaluated prospectively. The median length of stay was 4 days, and the patients were classified into 2 groups: those with lengths of stay <= 4 days and those with lengths of stay > 4 days. Patients with longer lengths of stay had a significantly higher cancer antigen 125 level of 114 U/mL (range, 9-298 U/mL) than did those with a shorter length of stay (19 U/mL; range; 3-68) (P < 0.001). The optimal cutoff level of cancer antigen 125 in the prediction of length of stay was > 48 U/mL, with a specificity of 95.8% and a sensitivity of 96% (area under the curve, 0.979; 95% confidence interval [CI], 0.953-0.992). In the multivariate logistic regression model, cancer antigen 125 > 48 U/mL on admission (odds ratio=4.562; 95% CI, 1.826-11.398; P=0.001), sodium level (P< 0.001), creatinine level (P=0.009), and atrial fibrillation (P=0.015) were also associated with a longer length of stay after adjustment for variables found to be statistically significant in univariate analysis and correlated with cancer antigen 125 level. In addition, it appears that in a cohort of patients with acute decompensated heart failure, cancer antigen 125 is independently associated with prolonged length of stay.