<p>This single-center prospective cohort study establishes ultrafiltration rate variability (quantified by coefficient of variation, UFRCV) as an independent predictor of all-cause and cardiovascular mortality in maintenance hemodialysis patients. While absolute ultrafiltration rate thresholds represent established risk factors, dynamic fluid removal fluctuations remain prognostically uncharacterized. We longitudinally monitored ultrafiltration rate patterns during a 90-day observation period in 202 hemodialysis patients (median follow-up: 38.7 months). Stratification by median UFRCV (0.187) revealed significantly reduced survival among patients with elevated variability. This association demonstrated particular clinical significance in elderly individuals (&gt; 60 years), those with recurrent intradialytic hypotension, and subjects exhibiting elevated predialysis systolic blood pressure variability. Notably, UFRCV exhibited stronger mortality prediction in patients with lower mean ultrafiltration volumes (&lt; 2469 mL), indicating that current static ultrafiltration rate targets inadequately reflect dynamic hemodynamic vulnerability. These findings underscore the imperative to integrate ultrafiltration rate variability metrics into personalized volume management frameworks—a parameter currently absent from dialysis adequacy guidelines. Collectively, UFRCV assessment emerges as a critical indicator of subclinical hemodynamic compromise, providing pivotal insights for refining hemodynamic risk stratification in maintenance hemodialysis populations.</p>