Health-related quality of life (HRQoL) for patients following myocardial infarction (MI) is frequently impaired. We investigated the association of baseline and changes in HRQoL with mortality following MI. Nationwide longitudinal study of 9474 patients admitted to 77 hospitals in England as part of the Evaluation of the Methods and Management of Acute Coronary Events study. Self-reported HRQoL was collected using EuroQol EQ-5D-3L during hospitalization and at 1, 6, and 12 months following discharge. The data was analysed using flexible parametric and multilevel survival models. Of 9474 individuals with MI, 2360 (25%) were women and 2135 (22.5%) died during the 9-year follow-up period. HRQoL improved over 12 months (baseline mean, mean increase: EQ-5D 0.76, 0.003 per month; EQ-VAS 69.0, 0.5 per month). At baseline, better HRQoL was inversely associated with mortality [Hazard ratio (HR) 0.55, 95% CI 0.47-0.63], and problems with self-care (HR 1.73, 1.56-1.92), mobility (1.65, 1.50-1.81), usual activities (1.34, 1.23-1.47), and pain/discomfort (1.34, 1.22-1.46) were associated with increased mortality. Deterioration in mobility, pain/discomfort, usual activities, and self-care over 12 months were associated with increased mortality (HR 1.43, 95% CI 1.31-1.58; 1.21, 1.11-1.32; 1.20, 1.10-1.32; 1.44, 1.30-1.59, respectively). After MI, poor HRQoL at baseline, its dimensions, and deterioration over time are associated with an increased risk of mortality. Measuring HRQoL in routine clinical practice after MI could identify at-risk groups for interventions to improve prognosis.