Positive energy balance is the major cause of obesity, and chronic stress may be a contributory factor. The authors examined cumulative work stress, using the Job Strain Questionnaire on four occasions, as a predictor of obesity in a prospective 19-year study of 6,895 men and 3,413 women (aged 35-55 years) in the Whitehall II cohort in London, United Kingdom (baseline: 1985-1988). A dose-response relation was found between work stress and risk of general obesity (body mass index > or =30 kg/m(2)) and central obesity (waist circumference >102 cm in men, >88 cm in women) that was largely independent of covariates. The imputed odds ratios of body mass index obesity for one, two, and three or more reports of work stress adjusted for age, sex, and social position were 1.17, 1.24, and 1.73 (trend p < 0.01), respectively. For waist obesity, the corresponding findings were 1.17, 1.41, and 1.61 (trend p < 0.01). Work stress effect was modestly attenuated after exclusion of obese individuals at baseline and further adjustments for smoking; intakes of dietary fiber, fruits and vegetables, and alcohol; and levels of physical activity during follow-up. This study provides prospective, population-based evidence that chronic work stress predicts general and central obesity.