This cross-sectional study investigates the relationship between the psychosocial work environment and cardiovascular disease (CVD) prevalence in a randomly selected, representative sample of 13,779 Swedish male and female workers. It was found that self-reported psychological job demands, work control, and co-worker social support combined greater then multiplicatively in relation to CVD prevalence. An age-adjusted prevalence ratio (PR) of 2.17 (95% CI-1.32, 3.56) was observed among workers with high demands, low control, and low social support compared to a low demand, high control, and high social support reference group. PRs of approximately 2.00 were observed in this group after consecutively controlling for the effects of age together with 11 other potential confounding factors. The magnitude of the age-adjusted PRs was greatest for blue collar males. Due to the cross-sectional nature of the study design, causal inferences cannot be made. The limitations of design and measurement are discussed in the context of the methodological weaknesses of the work stress field.