Although a previous randomized study showed that the use of atrial natriuretic peptide (carperitide) improved the long-term prognosis of patients with heart failure, its effect on short-term prognosis remains unclear. We retrospectively identified patients who were admitted to our tertiary-care center with acute decompensated heart failure (ADHF) between April 2009 and December 2013.We divided the eligible patients into two groups: patients who started receiving carperitide on the day of admission (carperitide group) and those who did not receive carperitide during hospitalization (control group). We compared the in-hospital mortality between the two groups using propensity scores derived from 40 baseline variables. We identified 879 eligible patients (mean age, 75.2 years; male, 56.7%), including 336 (38.2%) in the carperitide group and 543 (61.8%) in the control group. One-to-one propensity score matching created 177 pairs. Although the unmatched analysis found a significantly lower in-hospital mortality in the carperitide group than in the control group (3.3% vs. 7.9%, respectively, p = 0.005), the propensity score-matched analysis found no significant difference in in-hospital mortality between the two groups [4.0% vs. 5.1%, p = 0.609; risk difference, −1.1%, 95% confidence interval (CI), −5.5–3.2%]. Logistic regression analysis with adjustment for propensity scores also found no significant association between carperitide use and in-hospital mortality (adjusted odds ratio, 0.61; 95% CI, 0.29 to 1.28; p = 0.605). The present retrospective study showed that carperitide use as the initial treatment was not significantly associated with lower in-hospital mortality in patients with ADHF.