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Abstract Background In 1993, 1000 randomly selected employed Swedish men aged 45–50 years were invited to a nurse-led health examination with a survey on life style, fasting lab tests, and a 12-lead ECG. A repeat examination was offered in 1998. The ECGs were classified according to the Minnesota Code. Upon ethical approval, endpoints in terms of MI and death over 25 years were collected from Swedish national registers with the purpose of analyzing the independent association of ECG abnormalities as risk factors for myocardial infarction and death. Results Seventy-nine of 977 participants had at least one ECG abnormality 1993 or 1998. One hundred participants had a first MI over the 25 years. Odds ratio for having an MI in the group that had one or more ECG abnormality compared with the group with two normal ECGs was estimated to 3.16. 95%CI (1.74; 5.73), p value 0.0001. One hundred fifty-seven participants had died before 2019. For death, similarly no statistically significant difference was shown, OR 1.52, 95%CI (0.83; 2.76). Conclusions Our study suggests that presence of ST- and R-wave changes is associated with an independent 3–4-fold increased risk of MI after 25 years follow-up, but not of death. A 12-lead resting ECG should be included in any MI risk calculation on an individual level.