Abstract Background Although Westernized lifestyle was associated with increased coronary heart disease (CHD) morbidity and mortality in first and second generation Japanese Americans; CHD mortality was reported to be lower in them than whites. Risk profile of CHD for third and fourth generation Japanese Americans is not known. We compared progression of CIMT between third or fourth generation Japanese Americans and whites. Methods Population-based samples of 473 men (Japanese Americans=227 and whites=246) aged 40-49 years at baseline and free of clinical cardiovascular disease were examined for CIMT at baseline (2002-06) and follow-up (2007-13). CIMT was read centrally at the University of Pittsburgh. Analysis of covariance was used to compare annualized progression of CIMT between Japanese Americans and whites, adjusting for cardiovascular risk factors and baseline CIMT. Results Progression of CIMT was significantly greater in Japanese Americans than whites both before and after adjusting for covariates (mean in μm/year 95% confidence interval): 14.4 (12.3, 16.4) vs 9.8 (7.8, 11.7), P <0.05 and 15.1 (13.1, 17.1) vs 9.1 (7.2, 11.0), P <0.05, respectively. Age, total cholesterol/high-density lipoprotein-cholesterol, and diabetes in Japanese Americans and age, hypertension, and lipid medication in whites were significantly associated with progression of CIMT. Conclusions The significantly greater progression of CIMT in Japanese Americans than whites might suggest a higher burden of CHD in Japanese Americans than whites in the future. The current study identifies Japanese Americans as an important target group for prevention of CHD. Future research assessing carotid plaque in addition to CIMT is warranted.