OBJECTIVES: To estimate the association between the transition to daylight saving time and the risks of all cause and cause specific mortality in the US. DESIGN: Nationwide time series observational study based on weekly data. SETTING: US state level mortality data from the National Center for Health Statistics, with death counts from 50 US states and the District of Columbia, from the start of 2015 to the end of 2019. POPULATION: 13 912 837 reported deaths in the US. MAIN OUTCOME MEASURES: Weekly counts of mortality for any cause, and for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. RESULTS: During the study period, 13 912 837 deaths were reported. The analysis found no evidence of an association between the transition to spring daylight saving time (when clocks are set forward by one hour on the second Sunday of March) and the risk of all cause mortality during the first eight weeks after the transition (rate ratio 1.003, 95% confidence interval 0.987 to 1.020). Autumn daylight saving time is defined in this study as the time when the clocks are set back by one hour (ie, return to standard time) on the first Sunday of November. Evidence indicating a substantial decrease in the risk of all cause mortality during the first eight weeks after the transition to autumn daylight saving time (0.974, 0.958 to 0.990). Overall, when considering the transition to both spring and autumn daylight saving time, no evidence of any effect of daylight saving time on all cause mortality was found (0.988, 0.972 to 1.005). These patterns of changes in mortality rates associated with transition to daylight saving time were consistent for Alzheimer's disease, dementia, circulatory diseases, malignant neoplasms, and respiratory diseases. The protective effect of the transition to autumn daylight saving time on the risk of mortality was more pronounced in elderly people aged ≥75 years, in the non-Hispanic white population, and in those residing in the eastern time zone. CONCLUSIONS: In this study, transition to daylight saving time was found to affect mortality patterns in the US, but an association with additional deaths overall was not found. These findings might inform the ongoing debate on the policy of shifting daylight saving time.