Shift work is associated with increased cardiovascular morbidity and mortality. Whereas it has been suggested that continuous shifting of the circadian clock/sleep-wake cycle may have negative effects on health, there is very little experimental evidence to support such a hypothesis. Cardiomyopathic Syrian hamsters were either maintained on a fixed light-dark (LD) cycle (n = 31) or were subjected to a 12-h phase shift in the LD cycle on a weekly basis (n = 32). The duration of the life span was recorded for each animal. Chronic reversal of the external LD cycle at weekly intervals resulted in a significant decrease in the survival time in cardiomyopathic hamsters with the median life span being reduced by 11%. Disrupting normal circadian rhythmicity in an animal susceptible to early mortality due to cardiac disease results in a further decrease in longevity. The deleterious effects of the chronic phase shifts in the LD cycle in cardiomyopathic hamsters may be related to reports of increased cardiovascular morbidity and mortality in humans engaged in shift work.