<jats:sec><jats:title>Objective</jats:title><jats:p>To assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The global, prospective, observational TIGRIS Study enrolled 9126 patients 1–3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years’ follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years’ follow-up.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Among 8978 patients who completed the EQ-5D questionnaire, 52% reported ‘some’ or ‘severe’ problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years’ follow-up.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Clinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death.</jats:p></jats:sec><jats:sec><jats:title>Trial registration number</jats:title><jats:p>ClinicalTrials.gov Registry (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT01866904">NCT01866904</jats:ext-link>) (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov">https://clinicaltrials.gov</jats:ext-link>).</jats:p></jats:sec>