In characterizing sleep and circadian health, the day-to-day regularity of sleep-wake timing strongly predicts health outcomes, outperforming short sleep duration in prospective associations with mortality and new-onset disease. It is unknown whether biological (e.g., sleep and circadian physiology) and sociocultural (e.g., exposures that affect sleep-wake timing) sex differences lead to differences in day-to-day sleep-wake regularity or modify its prospective associations with health outcomes. Here, we present findings from a UK Biobank study of 506,582 person-days of accelerometer recordings across 73,647 middle-aged adults preceding 549,009 person-years of follow-up. We compared SRI scores between males and females and evaluated whether all-cause, cardiovascular, and cancer mortality differed across SRI groups by sex. Custom contrasts were used to compare estimated marginal means across specific SRI-sex combinations. Females were overrepresented among very high (SRI [≥]90) and underrepresented among very low (SRI