Objective: To assess the impact of class III obesity on outcomes and complications of transvaginal ultrasound-guided oocyte pickup (OPU). Design: Retrospective cohort study. Setting: Hospital-based fertility clinic. Patient(s): All women undergoing OPU procedures during autologous in vitro fertilization (IVF) and oocyte banking cycles, grouped by patient body mass index (BMI: <25, 25–29.9, 30–34.9, 35–39.9, ≥40 kg/m2). Intervention(s): Transvaginal OPU under conscious sedation. Main Outcome Measure(s): Sedation and procedure-related parameters and complications. Result(s): A total of 2,141 OPU procedures in 1,579 patients were analyzed, including 121 OPU procedures in 94 patients with BMI ≥40 kg/m2. There was a statistically significant increase in total fentanyl and midazolam doses and procedure duration as BMI increased. Compared with patients with BMI <25 kg/m2, those with BMI ≥40 kg/m2 were more likely to require additional sedation during the procedure (adjusted odds ratio [aOR] 1.99; 95% confidence interval [CI], 1.14–3.49). The rate of difficult access was 28.9% for procedures with BMI ≥40 kg/m2 compared with 5.2% with BMI <25 kg/m2 (aOR 7.57; 95% CI, 4.66–12.29). The OPU was incomplete due to inaccessible follicles through a transvaginal approach in 18.2% of procedures with BMI ≥40 kg/m2 compared with 1.3% with BMI <25 kg/m2 (aOR 16.94; 95% CI, 8.24–34.84). The rates of sedation and procedure-related complications were low, and none occurred in patients with BMI ≥40 kg/m2. Conclusion(s): There was no increased risk of complications for women with class III obesity undergoing OPU with conscious sedation. However, the operator was more likely to encounter difficult access and to incompletely aspirate follicles through a transvaginal approach.