In the acute heart failure (AHF) setting, the usefulness of C-reactive protein (CRP) at admission as a risk marker is challenged by the possible confounding effect of an acute-phase response. We thus evaluated the relation of CRP level at discharge (i.e., after stabilization of AHF) with subsequent postdischarge outcome in patients hospitalized for AHF. The acute decompensated heart failure syndromes study prospectively registered 4,269 hospitalized AHF patients with data on CRP levels at discharge. The median CRP level was 3.1 mg/L (interquartile range 1.1 to 9.5 mg/L). Within 120 days after discharge, only CRP levels in the fourth quartile (≥9.6 mg/L) were independently associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.68) according to multivariable models with first-quartile (≤1.1 mg/L) as the reference. However, the HR for CRP levels in the fourth quartile decreased markedly with time, and CRP levels in the second (1.2 to 3.1 mg/L) and third (3.2 to 9.5 mg/L) quartiles were independently associated with poorer survival after the 120-day follow-up period (adjusted HR, 1.41 and 1.63, respectively). In addition, only CRP levels in the third quartile were independently associated with the composite end point of all-cause death and readmission for AHF after the 120 days of long-term follow-up (adjusted HR, 1.31). In conclusion, our results suggest that a modestly elevated CRP level (approximately 3 to 10 mg/L) at discharge had unique long-term prognostic implications in hospitalized patients with AHF.