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Objectives Elevated resting heart rate (RHR) predicts mortality in middle-aged and older adults, primarily through cardiovascular disease (CVD). Whether RHR predicts mortality in young adults, which causes of death are involved and whether the association replicates are unclear. In young US adults, who fall below the starting age of current cardiovascular risk tools, we examined RHR and all-cause and cause-specific mortality across two cohorts.Methods We analysed 3291 adults aged 20–49 years from National Health and Nutrition Examination Survey (NHANES) 1999–2004 (primary cohort) linked to mortality through 2019 (median follow-up 17.8 years; 120 deaths) with replication in 8941 adults from NHANES III (1988–1994; 1317 deaths; median follow-up 27.6 years; temporal replication). RHR and heart rate reserve (HRR) were modelled per 10 beats per minute increment using Cox regression adjusted for demographic, lifestyle and comorbidity covariates.Results Each 10 beats per minute higher RHR was associated with higher all-cause mortality (primary cohort: HR, 1.26; 95% CI 1.07 to 1.50; validation: HR, 1.17; 95% CI 1.12 to 1.22). In the primary cohort most deaths (99 of 120) were non-CVD; the CVD-specific analysis was underpowered (21 deaths; HR, 1.15; 95% CI 0.77 to 1.71). In validation, RHR predicted non-CVD (HR, 1.17; 95% CI 1.11 to 1.23) and CVD (HR, 1.18; 95% CI 1.08 to 1.29) mortality about equally. The association strengthened with age, emerging by the early-to-mid 30 s in both cohorts, before the starting age of current risk tools. HRR, measured under submaximal conditions, was not associated with any outcome.Conclusions In young US adults, elevated resting heart rate, a free and routinely measured vital sign, predicts long-term mortality across two cohorts, marking broad survival vulnerability rather than cardiovascular risk alone. Detectable in the early-to-mid 30 s, below the starting age of current cardiovascular risk tools, resting heart rate may flag at-risk young adults before these tools apply. Submaximal HRR carried no prognostic value.