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Following an earlier study of incidence and mortality of ischemic heart disease (IHD) published in 2010, a second analysis has been conducted based on an extended cohort and five additional years of follow-up. The cohort includes 18,763 workers, of whom 25% were females, first employed at the Mayak PA in 1948–1972 and followed up to the end of 2005. Some of these workers were exposed to external gamma rays only, and others were exposed to a mixture of external gamma-rays and internal alpha-particle radiation. A total of 6,134 cases and 2,629 deaths from IHD were identified in the study cohort. A statistically significant increasing trend was found with total external gamma-ray dose in IHD incidence (ERR/Gy 0.099; 95% CI: 0.045–0.153) after adjusting for non-radiation factors. This value reduced slightly when adjusting for internal liver dose. There was no statistically significant increase trend for internal liver dose in IHD incidence. These findings were consistent with an earlier study. New findings in IHD incidence revealed a statistically significant decrease in IHD incidence among workers exposed to external gamma-rays doses of 0.2–0.5 Gy in relation to the external doses below 0.2 Gy. This decreased risk is heavily influenced by female workers. This finding has never been reported in other studies, and the results should be treated with caution. The findings for IHD mortality are similar to those results in the earlier analysis; there was no statistically significant trend with external gamma-ray dose or for internal liver dose after adjustment for external dose. The risk estimates obtained from these analyses of IHD incidence and mortality in relation to external gamma-rays in the cohort of Mayak workers are generally compatible with those from other large occupational radiation worker studies and the Japanese atomic bomb survivors.