Health professions are characterized by high stress and risk of burnout, as a consequence of the many situations and tasks doctors and nurses have to face in their daily work activities. Aim of present study is to present the first validation of the Health Professions Stress and Coping Scale (HPSCS), a new instrument created to assess the stress and coping strategies doctors and nurses adopt in facing 24 specific situations characterizing their job. The HPSCS is designed to evaluate four coping mechanisms: focus on problem, focus on emotion, search of social support, and avoidance. 64 doctors and 99 nurses belonging to various Italian hospitals participated to the study. Results showed the good capacity of the HPSCS to assess the level of stress perceived in specific job situations both for doctors and nurses. Doctors and nurses use different coping strategies; however when the stress is high, both are more prone to adopt disadaptive mechanisms. Finally we identified four clusters of doctors and nurses, characterized by a different use of the two adaptive and the two disadaptive coping strategies.