© 2019 Elsevier Inc. Objectives: In patients with heart failure, fluid alteration and low muscle strength frequently coexist because of their reduced physical activity and sedentary behavior; however, few studies have evaluated the effects of this coexistence on the prognosis of these patients. The aim of this study was to examine the independent association between fluid alteration and the low handgrip strength (HGS) index with mortality in patients with chronic heart failure. Methods: This observational study included 546 (53.3% male) stable outpatients with heart failure. The presence of an abnormal fluid distribution was determined with a bioelectrical impedance ratio (200/5 kHz) ≥0.85. Handgrip strength (HGS) was measured with a hand dynamometer, and the HGS index was calculated by dividing the HGS (kg) by the squared height (meters). A low HGS index was defined if men had <10.1 and women <7.95 kg/m2. The primary outcome was all-cause mortality. Results: The mean age of the study population was 60.75 ± 17 y, and 30% were classified with a low HGS index, 9.5% with an abnormal fluid distribution, and 29% with both. During the 36 mo of follow-up, 16.5% of the participants reached the endpoint. In men but not in women, coexistence of a low HGS index and abnormal fluid distribution were independently associated with all-cause mortality with a hazard ratio of 2.8 (95% confidence interval, 1.25–6.4; P = .0.01). Conclusions: In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality.