<jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>The prognostic impact of platelet distribution width (PDW), which is a specific marker of platelet activation, has been unclear in patients with heart failure (HF).</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods and results</jats:title> <jats:p>We conducted a prospective observational study enrolling 1,746 hospitalized patients with HF. Patients were divided into tertiles based on levels of PDW: 1<jats:sup>st</jats:sup> (PDW < 15.9 fL, n = 586), 2<jats:sup>nd</jats:sup> (PDW 15.9–16.8 fL, n = 617), and 3<jats:sup>rd</jats:sup> (PDW ≥ 16.9, n = 543) tertiles. We compared baseline patients’ characteristics and post-discharge prognosis: all-cause death; cardiac death; and cardiac events. The 3<jats:sup>rd</jats:sup> tertile showed the highest age and levels of B-type natriuretic peptide compared to other tertiles (1<jats:sup>st</jats:sup>, 2<jats:sup>nd</jats:sup>, and 3<jats:sup>rd</jats:sup> tertiles; age, 69.0, 68.0, and 70.0 years old, P = 0.038; B-type natriuretic peptide, 235.2, 171.9, and 241.0 pg/mL, P < 0.001). Left ventricular ejection fraction was equivalent among the tertiles. In the Kaplan-Meier analysis, rates of all endpoints were the highest in the 3<jats:sup>rd</jats:sup> tertile (log-rank P < 0.001, respectively). The Cox proportional hazard analysis revealed that the 3<jats:sup>rd</jats:sup> tertile was associated with adverse prognosis (all-cause death, hazard ratio [HR] 1.716, P < 0.001; cardiac death, HR 1.919, P < 0.001; cardiac event, HR 1.401, P = 0.002).</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Conclusions</jats:title> <jats:p>High PDW is a novel predictor of adverse prognosis in patients with HF.</jats:p> </jats:sec>