Past measurement of vitality has included both emotional and physical components. Since aspects of physical vitality such as fatigue can be indicative of physical illness, the usefulness of existing measures of vitality to predict health is limited. This research was designed to examine the psychometric properties of a new Mental Vitality Scale and to test its associations with measures of cardiovascular health over the course of 2 years. The measure of mental vitality was administered in a two-part study using three different samples. In part 1, the reliability and validity of the scale was assessed with a student and a clinic sample. In part 2, medical data on mental and physical health were abstracted over a two-year period from 1041 patient records from a multi-specialty medical practice, and mental vitality assessed through a mailed questionnaire. The findings indicate that the Mental Vitality Scale is a valid and reliable questionnaire for measuring this construct. Mental vitality was also associated with reduced odds of several cardiovascular outcomes and prospective analyses suggest that mental vitality may serve a protective function in the development of cardiovascular disease. The results lend support for the importance of mental vitality as a construct that may be relevant for considering resilience in relation to cardiovascular disease.