ABSTRACT: Although soy food has been recommended because of its presumed cardiovascular benefits, the long-term prospective association between habitual soy food intake and cardiovascular disease mortality remains unclear. This study aimed to evaluate the relation of soy protein and isoflavone intake with the risk of cardiovascular disease mortality in middle-aged and older Chinese adults residing in Singapore. The Singapore Chinese Health Study is a population-based study that recruited 63,257 Chinese adults aged 45-74 y from 1993 to 1998. Usual diet was measured at recruitment by using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage until 31 December 2011. Cox proportional hazards models were used to calculate HRs, with adjustment for potential confounders. The median intake was 5.2 g/d for soy protein, 15.8 mg/d for soy isoflavones, and 87.4 g/d for soy expressed as tofu equivalents. We documented 4780 cardiovascular deaths during 890,473 person-years of follow-up. After adjustment for sociodemographic, lifestyle, and other dietary factors, soy protein intake was not significantly associated with cardiovascular disease mortality: HRs (95% CIs) were 1.00 (reference), 1.02 (0.94, 1.11), 1.02 (0.93, 1.11), and 1.06 (0.97, 1.17) for increasing quartiles of soy protein (P-trend = 0.24). Similarly, no significant association was observed for soy isoflavones and total tofu equivalents and when deaths from coronary heart disease (n = 2697) and stroke (n = 1298) were considered separately. When stratified by sex, HRs for cardiovascular disease mortality across quartiles of soy protein were 1.00, 1.00, 1.05, and 1.16 (95% CI: 1.03, 1.31) in men (P-trend = 0.02) and 1.00, 1.01, 0.96, and 0.95 (95% CI: 0.81, 1.10) in women (P-trend = 0.31), although the interaction was not significant (P-interaction = 0.12). In conclusion, soy intake was not significantly associated with risk of cardiovascular disease mortality in the Chinese population. However, a slightly increased risk associated with high soy protein intake in men cannot be excluded and requires further investigation.