Background: Work stress has been recognized as an important factor having negative effect not only on the health of the workers but also on their productivity; and away from its economic impact, stress of the workers in the medical field might threaten the safety of the patients. Despite its apparent effects, few researches have been conducted worldwide and in Saudi Arabia in particular. Objectives: Therefore, the current study aimed at exploring the magnitude of the work stress, its causes and impact on productivity among female physicians and nurses working in Emergency Room (ER) in Ministry of Health (MOH) hospitals. Material and methods: Accordingly, through cross sectional design, all female physicians and nurses in ER departments in three MOH hospitals were invited to be enrolled in the study and filling a pre-designed self-administered valid questionnaire. Results: One hundred and fifteen (18 physicians and 97 nurses) responded and filled down the questionnaires. The mean score of work stress accounted for 2.92+0.67 out of 5, and it was found to be significantly higher among Saudis than non Saudis p<0.05. The main identified source of work stress is dealing with patients who lose temper easily, and the mean scores for each item reflecting sources of stress was higher among physicians than nurses especially those related to dealing with tempered patients, lack of appropriate appreciations, short breaks and having to adapt with negative decisions which showed statistically significant differences between the two groups. Conclusion and recommendations: Working in ER is stressful for female physicians and nurses for many reasons which are mostly modifiable. It was recommended that deliberate efforts should be made to increase the number of working physicians in ER departments and to settle appropriate system for providing them with incentives in the form of training and financial increments.