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The aim of this study was to investigate whether information on both cardiorespiratory fitness (CRF) and exercise-induced ST segment depression improves the prediction of sudden cardiac death (SCD) in men.The study was based on a population sample of 2328 men aged 42–60 years, who were followed up for on average 19 years. CRF was assessed with maximal exercise test using respiratory gas analysis, expressed in metabolic equivalents (METs) and dichotomised at eight METs. Exercise-induced ST segment depression was defined as 1 mm ST segment depression in ECG.Altogether 165 SCDs occurred during the follow-up. Men with low CRF (<8 METs) and exercise-induced ST segment depression had 4.8-fold (95% CI 2.9 to 7.9) higher risk of SCD than men with high CRF and without exercise-induced ST segment depression (p=0.013 for interaction) after adjustment for other cardiovascular risk factors. Men with high CRF and exercise-induced ST segment depression did not have a statistically significantly higher risk of SCD (HR 1.9, 95% CI 0.9 to 3.8) than men with high CRF and without exercise-induced ST segment depression.The combination of low CRF and exercise-induced ST segment depression was associated with a markedly increased risk of SCD in men.