Patients with heart failure (HF) reportedly have activated platelets with increased platelet distribution width (PDW) and mean platelet volume (MPV), which lead to thrombotic events. These platelet indices are easily measured by routine blood tests and have been proposed as potential markers of cardiac events. We performed the present study to clarify whether platelet indices correlate to the severity of HF and to the prognosis of patients with congenital heart disease (CHD). We performed a retrospective single-center study including 400 patients with CHD [median age, 34 years (range 12–76); 49% males] hospitalized between 2014 and 2017. We assessed their clinical data, correlation between platelet indices and severity of HF, and prognosis of HF-related hospitalization and thrombus formation. In multivariate analysis, a significant correlation was found between PDW and logBNP (log-transformed brain natriuretic peptide; r = 0.30, p < 0.001), as well as between MPV and logBNP (r = 0.24, p < 0.001). After treatment for heart failure, a significant reduction was found in PDW (average value before treatment: 14.2; after: 13.2, p = 0.017). In multivariate logistic regression analysis, PDW [hazard ratio (HR) 1.365; 95% confidence interval (CI) 1.005–1.768] and MPV (HR 1.472; 95% CI 1.055–2.052) were predictors of HF-related hospitalization. Similarly, PDW (HR 1.998; 95% CI 1.461–2.630) and MPV (HR 1.792; 95% CI 1.155–2.781) were predictors of thrombus formation. Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with CHD.