We examined the associations between a sense of purpose and all-cause mortality by gender and race/ethnicity groups. Data were from the Health and Retirement Study, a nationally representative cohort study of U.S. adults aged >50 (n = 13,159). Sense of purpose was self-reported at baseline (2006/2008), and risk of all-cause mortality was assessed over an 8-year follow-up period. We also formally tested for potential effect modification by gender and race/ethnicity. We observed the associations between higher purpose and lower all-cause mortality risk across all gender and race/ethnicity groups. There was modest evidence that the highest level of purpose (versus lowest quartile) was associated with even lower risk of all-cause mortality among women (risk ratio = 0.66, 95% confidence interval: 0.56, 0.77) compared to men (risk ratio = 0.80, 95% confidence interval: 0.69, 0.93; p-value for multiplicative effect modification =0.07). However, we observed no evidence of effect modification by race/ethnicity. Having a higher sense of purpose appears protective against all-cause mortality regardless of gender and race/ethnicity. Purpose, a potentially modifiable factor, might be a health asset across diverse populations.