OBJECTIVE To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. METHODS This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. RESULTS Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]). CONCLUSIONS In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.