To assess the effects of site and route of morcellation on perioperative outcomes in patients with body mass index (BMI) ≥40 (WHO class 3 obesity). We performed a retrospective cohort study of women with BMI ≥40 who required tissue morcellation during laparoscopic hysterectomy at an academic tertiary care center between January 2006 and March 2018. Morcellation site was either vaginal or abdominal, with abdominal sites including suprapubic, umbilical, or lateral locations. Morcellation route was either manual or electromechanical. The primary outcome was perioperative complication, classified by Clavien-Dindo grade (minor complications grade I to II, major complications grade III to V). Secondary outcomes included surgical time, surgical blood loss, and hospital length of stay. Chi-square, Fisher’s exact, and Wilcoxon tests were used where appropriate. Multivariable logistic regression was used to estimate the association between site or route of morcellation and perioperative complications. Of 96 identified patients, 57 (59.4%) underwent abdominal morcellation and 39 (40.6%) underwent vaginal morcellation. Abdominal morcellation included 38 (66.7%) umbilical, 11 (19.3%) suprapubic, and 8 (14.0%) lateral sites. The average BMI was 45.3 ± 6.8 kg/m2. There were no differences in age, hysterectomy year, BMI, parity, prior abdominal surgery, or medical comorbidities between abdominal and vaginal morcellation sites. Mean specimen weight was significantly larger for patients who underwent abdominal (829.0 ± 755.6g) versus vaginal morcellation (467.3 ± 334.8g, p<0.01), without a difference in surgical time (267.4 vs 237.4 min, p=0.17), surgical blood loss (196.4 vs 133.3mL, p=0.74), and hospital length of stay (2.0 vs 2.4 days, p=0.12). There was a nonsignificant trend towards increased perioperative complications in the vaginal versus abdominal morcellation group (33.3% vs 21.1%, p=0.18), with associated differences in minor complications (28.2% vs 12.3%, p=0.05). There was no difference in major complications between vaginal and abdominal morcellation (7.0% vs 5.1%, p>0.99). No difference was found for perioperative complications between electromechanical and manual morcellation (37.8% vs 25.3%, p=0.16). After controlling for hysterectomy year, race, specimen weight, parity, and BMI, there was no difference in perioperative complications between abdominal versus vaginal sites (aOR 0.52, 95% CI 0.17-1.55) or manual versus electromechanical routes (aOR 0.55, 95% CI 0.18-1.71) of morcellation. In women with class 3 obesity, abdominal morcellation was associated with a significantly larger specimen size without any increase in perioperative complications compared to vaginal morcellation. Manual versus electromechanical morcellation had no significant difference in perioperative outcomes.