Background Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is associated with mortality and adverse outcome in selected populations with cardiovascular disease. It is scarcely known whether RDW is associated with incident myocardial infarction (MI). We aimed to investigate whether RDW was associated with risk of first‐ever MI in a large cohort study with participants recruited from a general population. Methods and Results Baseline characteristics, including RDW, were collected for 25 612 participants in the Tromsø Study in 1994–1995. Incident MI during follow‐up was registered from inclusion through December 31, 2010. Cox regression models were used to calculate hazard ratios with 95% confidence intervals for MI, adjusted for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets, and other traditional cardiovascular risk factors. A total of 1779 participants experienced a first‐ever MI during a median follow‐up time of 15.8 years. There was a linear association between RDW and risk of MI, for which a 1% increment in RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to 1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI, 1.34 to 2.20). All effect estimates were essentially similar after exclusion of participants with anemia (n=1297) from the analyses. Conclusion RDW is associated with incident MI in a general population independent of anemia and cardiovascular risk factors.