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Background: Ultrafiltration (UF) during hemodialysis is typically prescribed as a fixed treatment goal and delivered using a largely constant ultrafiltration rate throughout the session. We evaluated whether Adaptive Ultrafiltration (Adaptive UF), a physiological closed-loop control strategy guided by continuous relative blood volume (RBV) monitoring, could improve RBV target attainment while individualizing fluid removal within predefined treatment constraints. Methods: We performed a paired patient-specific in silico study using 119,472 historical hemodialysis treatments from 11,246 U.S. patients. Treatment-specific plasma refill rate profiles were derived from recorded RBV and ultrafiltration data. For each historical treatment, a corresponding Adaptive UF treatment was simulated and compared with the corresponding originally delivered treatment. Outcomes included the percentage of time within a predefined favorable RBV target region, UF delivery, and operational performance. Results: Mean time within the RBV target region increased from 36.3% with historically delivered treatments to 56.4% with Adaptive UF, showing an absolute improvement of 20.2 percentage points (95% CI, 19.9-20.5); target attainment improved in 90.0% of patients. Mean area outside the target range decreased from 280.7 to 139.5 RBV %-minutes. Mean achieved UF volume increased by 296.4 mL, although treatment-level UF delivery was bidirectional, increasing in 83.1% and decreasing in 16.9% of treatments. UF rates remained below 13 mL/kg/h in all simulations, and 99.4% of treatments remained within predefined UF volume limits. Conclusions: Adaptive UF improved intradialytic RBV target attainment and individualized UF delivery within predefined treatment constraints. Prospective studies are required to determine whether these physiological improvements translate into clinical benefit.