Objectives Associations between shift work, chronic psychosocial work stress, and 2 important cardiovascular risk factors, hypertension and atherogenic lipids were studied.The hypothesis was tested that psychosocial work stress, as defined by the model of effort-reward imbalance, mediates the effects of shift work on cardiovascular risk. Methods Altogether 2288 male participants aged 30-55 years in the baseline screening of the Swedish WOLF (work organization, lipids, and fibrinogen) study underwent a clinical examination and answered a standardized questionnaire measuring shiftwork schedules, effort-reward imbalance at work, and health-adverse behavior. Results In addition to the direct effects of shift work on cardiovascular risk, mediating effects of effort-reward imbalance at work were found. The respective odds ratios (OR) ranged from 2.18 to 2.27 for hypertension, and from 1.34 to 1.45 for atherogenic lipids. While the effects remained significant after extensive confounder control concerning hypertension, part of the observed effect on atherogenic lipids was due to behavioral influences. Conclusions Despite obvious limitations, the results indicated that a stressful psychosocial work environment acts as a mediator of health-adverse effects of shift work on hypertension and, partly, atherogenic lipids. In terms of occupational health the findings call for a more comprehensive assessment of the health risks associated with shift work.