Background and Objective <p>Obesity can alter the physiological profile of individuals, potentially impacting the pharmacokinetics of anesthetic agents. This study compared the pharmacokinetic profiles of lidocaine and its metabolites between obese patients and normal-weight patients following a single intravenous bolus during surgical operation, to inform dosing strategies for the obese Chinese population.</p> Methods <p>Twenty-nine obese patients scheduled for laparoscopic sleeve gastrectomy and 29 normal-weight patients for laparoscopic cholecystectomy were enrolled. Lidocaine (2%, 1.5 mg/kg) was administered intravenously to obese patients and normal-weight patients on the basis of adjusted body weight (ABW) and total body weight, respectively. Plasma samples were collected to analyze the pharmacokinetic profiles of lidocaine and its metabolites. Adverse events (AEs) were recorded throughout the study.</p> Results <p>Obese patients had a significantly longer half-life for lidocaine (2.27 ± 0.69 h vs 0.94 ± 0.16 h, <i>p</i> &lt; 0.0001), a higher volume of distribution (105 ± 27.3 L vs 54.9 ± 14.0 L, <i>p</i> &lt; 0.0001), and a lower clearance (33.6 ± 9.08 L/h vs 40.5 ± 8.67 L/h, <i>p</i> = 0.008) compared to normal-weight patients. Although exposure to lidocaine was similar between groups within 2 hours, obese patients had lower metabolite concentrations due to decreased metabolic capacity. The plasma concentrations in all patients remained below the toxic concentration of 5 μg/mL, and no serious lidocaine-related AEs were reported.</p> Conclusions <p>Obesity significantly affects the pharmacokinetics of lidocaine and its active metabolites, and administering lidocaine intravenously via ABW is safe and reasonable for obese patients.</p> Clinical Trial Registration <p>ChiCTR2200064980, 25 October 2022.</p>