OBJECTIVES: Assessing handgrip strength (HGS) asymmetry may provide insights into HGS as a prognostic assessment of strength capacity and vitality. This study sought to determine the associations of HGS asymmetry and weakness on time to mortality in aging Americans. DESIGN: Longitudinal panel. SETTING: Secondary analyses of data from participants aged ≥50 years from the 2006‒2014 waves of the Health and Retirement Study. PARTICIPANTS: The analytic sample included 19,325 Americans who identified hand dominance and had measures of HGS for both hands in a single wave. MEASURES: A handgrip dynamometer was used to measure HGS. Men and women who were considered weak had HGS <26 kg and <16 kg, respectively. The highest HGS values from the dominant and nondominant hands were used to calculate HGS ratio: (nondominant HGS/dominant HGS). Those with HGS ratio <0.90 or >1.10 had any HGS asymmetry. Moreover, participants with HGS ratio <0.90 had dominant HGS asymmetry, whereas those with HGS ratio >1.10 had nondominant HGS asymmetry. The National Death Index and postmortem interviews verified date of death. Covariate-adjusted Cox models were used for analyses. RESULTS: Those with any HGS asymmetry had a 1.10 [95% confidence interval (CI) 1.03‒1.17] higher hazard for mortality, while those with weakness had a 1.44 (CI 1.32‒1.58) higher hazard for mortality. Likewise, participants with dominant HGS asymmetry had a 1.11 (CI 1.03‒1.18) higher hazard for mortality, and those with weakness had a 1.45 (CI 1.32‒1.58) higher hazard for mortality; however, the association was not significant for those with nondominant HGS asymmetry (hazard ratio: 1.07; CI 0.96‒1.18). CONCLUSIONS AND IMPLICATIONS: HGS asymmetry and weakness are markers of impaired strength capacity that independently accelerate time to mortality, but the magnitude of these associations was more prominent for weakness. Nevertheless, assessments of asymmetric HGS are a simple adjunct analysis that may show promise for increasing the prognostic value of handgrip dynamometers.