To describe the perioperative outcomes of various modes of myomectomy (abdominal [AM], laparoscopic [LM], or robotic [RM]) in cases of extreme myoma burden. Design: Retrospective cohort study (Canadian Task Force classification II-2). Setting: A tertiary academic center in Boston, Massachusetts. Patients: All women who underwent an AM, LM, or RM for extreme myoma burden, defined as representing the upper quartile for specimen weight (≥434.6 g) or myoma count (≥7 myomas), between 2009 and 2016. Interventions: Baseline demographics and perioperative outcomes were collected from review of medical records, including estimated blood loss, operative time, length of stay, and complications. Univariate linear and logistic regression analyses were conducted. Measurements and Main Results: During the study period 659 women underwent myomectomy for extreme myoma burden; 47.2% of cases were AM, 28.1% LM, and 24.7% RM. Overall myoma burden differed across the 3 routes and was greatest in the AM group (mean weight: 696.2 § 784.5 g for AM vs 586.6 § 426.1 g for LM and 586.6 § 426.1 g for RM; mean number: 16.8 § 15.0 for AM vs 7.2 § 7.0 for LM and 6.7 § 4.7 for RM; p <.001 for both). The 3 routes differed in operative time and length of stay, with RM having the longest operative time (mean, 239.7 minutes; p <.001) and AM the longest length of stay (mean, 2.2 § .9 days; p <.001). Other perioperative outcomes were similar across the surgical approaches. Increasing myoma burden was associated with an increased risk of perioperative complications for all surgical approaches, with a threshold of 13 myomas associated with an almost 2-fold higher risk of perioperative complications (odds ratio, 1.77; 95% confidence interval, 1.17−2.70; p = .009). Cumulative incidence of perioperative complications with increasing specimen weight was greater in the RM cases as compared with AM (p = .002) or LM (p = .020), whereas the cumulative incidence of perioperative complications with increasing myoma count was lowest with AM compared with LM (p <.001) or RM (p <.001). Conclusion: Myomectomy for extreme myomas is feasible using an abdominal, laparoscopic, or robotic approach. Increased myoma burden is associated with an increased risk of perioperative complications. A threshold of 13 myomas was associated with an almost 2-fold higher risk of perioperative complications for all modes. Perioperative complication outcomes were more favorable in AM or LM over RM with increased myoma weight and AM over LM or RM with increased myoma number.