Background: The association between ultrafiltration rate (UFR) and mortality may be affected by the muscle mass or volume status in hemodialysis (HD) patients. However, there is an absence of data regarding this association. Methods: We performed an observational study on patients (≥18 years old) who had been on HD for at least 3 months. A body composition monitor (BCM) was used for baseline bioimpedance analysis measurement. The primary composite outcome was defined as the time to death or the first cardiovascular event. Results: The median (interquartile range) UFR, volume excess measured by the BCM, and lean tissue index (LTI) (calculated as lean tissue mass/height<sup>2</sup>) were 11.4 (8.0–15.0) mL/h/kg, 2.4 (1.4–4.1) L, and 12.5 (10.4–14.4) kg/m<sup>2</sup>, respectively. During 284 person-years of follow-up, the primary outcome occurred in 44 of the 167 patients (26%). Higher UFR was associated with an increased outcome of death or cardiovascular event; the adjusted hazard ratio (HR) was 1.044 (95% confidence interval [CI]: 1.006–1.083). This association remained consistent even after adjusting for volume excess. However, the association between UFR and the primary outcome was modified by LTI ( p<sub>interaction</sub> = 0.027); the association was significant in patients with LTI < 12.5 kg/m<sup>2</sup>, and the HR (95% CI) was 1.050 (1.001–1.102). Conclusion: Higher UFR was associated with an increased risk of a composite outcome of death or cardiovascular event regardless of volume status in HD patients. However, muscle mass may modify the association between higher UFR and increased risk of a composite outcome.