Abstract Background Women comprise nearly half of the labor force in our society, but the impact of the occupational psychical activity on women’s heart health in later life was unclear. We conducted a case-cohort study to assess the association of occupational physical activity (OPA), alone and jointly with leisure-time physical activity (LTPA) and risk of coronary heart disease (CHD). Methods We included women enrolled in Women’s Health Initiative Observational Study who provided an occupational history at baseline and were followed until 2013 for the first occurrence of myocardial infarction or death from CHD (mean age ± SD = 63.4 ± 7.2). A total of 5,243 women free of CHD at baseline were randomly selected into a subcohort and 3,421 CHD events were adjudicated during follow-up. Through linkage of Standard Occupational Classification codes to the Occupational Information Network, we assessed cumulative and most recent exposure of OPA. LTPA was assessed through Women’s Health Initiative’s physical activity questionnaire. Weighted Cox proportional hazard models were used to evaluate CHD risk. Results After adjustment for demographic and socioeconomic factors, levels of OPA were not associated with CHD risk. Compared with women with low OPA and high LTPA, women with moderate to high cumulative OPA and low LTPA had relative high CHD risk (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.26, 1.88 for moderate OPA and HR: 1.46. 95% CI: 1.20, 1.78 for high OPA). Discussion Results from this study suggest no overall association between lifetime OPA and CHD risk in women, but the impact of OPA varies by LTPA levels.