Sleep disturbances, including insufficient sleep duration and circadian misalignment, confer risk for cardiometabolic disease. Less is known about the association between the regularity of sleep/wake schedules and cardiometabolic risk. This study evaluated the external validity of a new metric, the Sleep Regularity Index (SRI), among older adults (n = 1978; mean age 68.7 ± 9.2), as well as relationships between the SRI and cardiometabolic risk using data from the Multi-Ethnic Study of Atherosclerosis (MESA). Results indicated that sleep irregularity was associated with delayed sleep timing, increased daytime sleep and sleepiness, and reduced light exposure, but was independent of sleep duration. Greater sleep irregularity was also correlated with 10-year risk of cardiovascular disease and greater obesity, hypertension, fasting glucose, hemoglobin A1C, and diabetes status. Finally, greater sleep irregularity was associated with increased perceived stress and depression, psychiatric factors integrally tied to cardiometabolic disease. These results suggest that the SRI is a useful measure of sleep regularity in older adults. Additionally, sleep irregularity may represent a target for early identification and prevention of cardiometabolic disease. Future studies may clarify the causal direction of these effects, mechanisms underlying links between sleep irregularity and cardiometabolic risk, and the utility of sleep interventions in reducing cardiometabolic risk.