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The effect of interscalene block (ISB) on pulmonary function of obese participants has not been investigated. The goal of this study is to assess the association of obesity (body mass index [BMI] >29 kg/m2 vs BMI <25 kg/m2) and change in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) after ISB in participants undergoing outpatient shoulder surgery.This prospective, observational cohort study compared obese (BMI >29 kg/m2) and normal-weight (BMI <25 kg/m2) groups undergoing ISB for ambulatory shoulder surgery, on preblock and postblock FVC and FEV1, at 30 minutes postblock and in the postanesthesia care unit (PACU). The primary outcome in this study was FVC% change (percentage change from preblock to postblock values of FVC) at 30 minutes postblock in the supine position. Secondary outcomes included FVC% change at PACU and in the sitting position, FEV1% change (percentage change from preblock to postblock values of FEV1), FVC, FEV1, incidence of diaphragmatic paresis, modified Borg scale for perceived dyspnea, Richmond Agitation-Sedation Scale scores for sedation, and intraoperative airway events.Fourteen participants were recruited to each group. The mean (standard deviation) BMI in the normal-weight and obese groups was 23 (1.7) and 33 (3.1) kg/m2, respectively. ISB success rate was 100%. All participants demonstrated hemidiaphragmatic paresis after ISB. Compared to the normal-weight group, in the sitting position, the obese group had a significant decrease in FVC% change at 30 minutes (−30 [10.5] vs −23 [7.2], P = .046) and an FEV1% change in the PACU (−40 [12.6] vs −27 [13.9], P = .02). No difference was found for measurements taken in the supine position. A repeated-measures analysis demonstrated that, adjusted for position, there is no significant group effect on FVC% change or FEV1% change from 30 minutes to PACU. The 2 groups were not different in terms of breathlessness and sedation at 30 minutes (P = .67, P = .48, respectively) and in the PACU (P = .69, P > .99, respectively) nor in the occurrence of intraoperative airway events (P > .99).ISB is associated with greater FVC and FEV1 reductions in obese participants undergoing shoulder surgery compared to normal-weight participants. Neither time (30 minutes versus PACU) nor position (sitting versus supine) affected this relationship. Despite these changes, obesity was not associated with increased clinical respiratory symptoms or events.