Work-related stress among physicians has been an issue of growing concern in recent years. How and why this may vary between different health care systems remains poorly understood. Using an established theoretical model (effort-reward imbalance), this study analyses levels of work stress among primary care physicians (PCPs) in three different health care systems, the United States, the United Kingdom and Germany. Whether professional autonomy and specific features of the work environment are associated with work stress and account for possible country differences are examined. Data are derived from self-administered questionnaires obtained from 640 randomly sampled physicians recruited for an international comparative study of medical decision making conducted from 2005 to 2007. Results demonstrate country-specific differences in work stress with the highest level in Germany, intermediate level in the US and lowest level among UK physicians. A negative correlation between professional autonomy and work stress is observed in all three countries, but neither this association nor features of the work environment account for the observed country differences. Whether there will be adequate numbers of PCPs, or even a field of primary care in the future, is of increasing concern in several countries. To the extent that work-related stress contributes to this, identification of its organizational correlates in different health care systems may offer opportunities for remedial interventions. Copyright 2010 Elsevier Ltd. All rights reserved.