INTRODUCTION: The relationships between grip strength asymmetry (GSA) and cardiovascular, respiratory, and cancer outcomes and all-cause mortality remains unclear. METHODS: Among 443132 UK Biobank participants enrolled from 2006-2010, GSA was defined as the ratio of left-hand grip strength (kg) to right-hand grip strength (kg)<
0.9 or>
1.1. Cox proportion model was employed to assess the associations of GSA with cardiovascular, respiratory, and cancer outcomes and all-cause mortality. Net reclassification improvement was assessed to evaluate the improvement in risk discrimination for outcomes after adding GSA into the model with established office-based risk factors. RESULTS: After a mean follow-up of 12.1 years, a total of 28478 (6.4%) deaths occurred. GSA was significantly associated with all-cause (hazard ratio [HR]: 1.096
95%CI: 1.070, 1.122), CVD (HR: 1.141
95%CI:1.071, 1.216), respiratory disease (HR: 1.183
95%CI:1.076, 1.301), COPD (HR: 1.284
95%CI: 1.087, 1.516), and cancer (HR: 1.051
95%CI: 1.017, 1.086) mortality. Significant associations of GSA with CVD (HR: 1.029
95%CI: 1.004, 1.054), respiratory disease (HR: 1.074
95%CI: 1.051, 1.103), COPD (HR: 1.123
95%CI: 1.038, 1.215), and colorectal cancer (HR: 1.051
95%CI: 1.037, 1.066) incidence were observed. Moreover, adding GSA into the model with established office-based risk factors significantly improved the ability to predict all-cause, CVD, and respiratory disease mortality. CONCLUSIONS: GSA was associated with a range of adverse health outcomes and may have clinical utility in predicting all-cause, CVD, and respiratory disease mortality. Further work is warranted to validate the clinical value of GSA assessment.