Background/Objective <p>Since muscle strength is modifiable and handgrip strength is a reliable biomarker for strength and mortality, exploring its association with mortality in individuals with severe obesity could help identify protective thresholds. We aimed to examine the dose-response association between handgrip strength and mortality in adults with severe obesity.</p> Subjects/Methods <p>We retrieved data from the Survey of Health, Ageing and Retirement in Europe (SHARE). Handgrip strength was measured in participants with a body mass index (BMI) higher than 40 kg/m². We used time-varying Cox proportional hazards regression to assess the association between handgrip strength and all-cause mortality risk. To account for potential non-linearity, we employed restricted cubic splines. We examined a total of 2229 adults (67.9% women; BMI of 43.8 kg/m²).</p> Results <p>We found an association between handgrip strength and mortality, showing a minimal and optimal dose for a reduced risk with 31 kg (HR 0.97, 95% CI, 0.96–0.99) and 36 kg (HR 0.90, 95% CI, 0.81–0.99), respectively. Additional sex-stratified analysis showed that lower than median levels of handgrip strength were gradually associated with increased risk in both men and women.</p> Conclusions <p>The association between handgrip strength and all-cause mortality in European adults with severe obesity highlights practical thresholds for risk reduction, with 31 kg as the minimum and 36 kg as the optimal strength level. In both men and women, handgrip strength below the median was linked to a gradual increase in mortality risk, emphasizing the importance of maintaining adequate muscle strength to improve health outcomes.</p>