The primary aim of this study was to investigate the guidance effect of the bispectral index (BIS) on the target plasma concentration (TPC) of propofol required for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). Second, to identify propofol consumption, recovery time, and adverse events. A total of 42 consecutive patients with liver cirrhosis and 43 consecutive patients with healthy livers were enrolled. Propofol was administered via a target control infusion (TCI) syringe pump (Marsh Model) at BIS 60-70. Patients were not intubated, were placed in the prone position, and underwent spontaneous breathing. Propofol TPCs (μg mL-1) and BIS values were recorded at T0 (baseline), T1 (5 min after induction), T2 (5 min into ERCP), T3 (15 min), T4 (30 min), and T5 (recovery). TPCs and propofol consumption were lower in patients with cirrhosis than in those without cirrhosis (T4: 2.7±0.5 vs. 3.3±0.4 μg mL-1), P=0.001, and 270.4±6.9 mg vs. 390.8±13.4 mg, P=0.001), respectively. Patients with cirrhosis required more time to recover (8.5±2 vs. 6.2±0.9 min, P=0.001), despite comparable ERCP durations (31.1±11.1 vs. 34±12.5 min, P=0.28). A significant decline in TPC values among patients with cirrhosis with time (T1: 3.3±0.3, T2: 3.1±0.3, T3: 2.9±0.4, T4: 2.7±0.5 μg mL-1, P=0.001), indicating a cumulative effect. One patient with cirrhosis required bag-mask ventilation, while three patients without cirrhosis were converted to general anaesthesia. Combining the TCI Marsh pharmacokinetic model with BIS monitoring lowered the TPC levels required for deep sedation in patients with cirrhosis compared with healthy patients and allowed for individual variations. The prone position in deeply sedated and non-intubated spontaneous breathing patients is not without the risk of hypoxia.