Although uterine size has been a previously cited barrier to minimally invasive hysterectomy, experienced gynecologic surgeons have been able to demonstrate that laparoscopic and vaginal hysterectomy is feasible with increasingly large uteri. By demonstrating that minimally invasive hysterectomy continues to have superior outcomes even with increased uterine weights, opportunity exists to meaningfully decrease morbidity, mortality, and cost associated with abdominal hysterectomy. We sought to determine if there is an association between uterine weight and posthysterectomy complications and if differences in that association exist across vaginal, laparoscopic, and abdominal approaches. We conducted a cohort study of prospectively collected quality improvement data from the American College of Surgeons National Surgical Quality Improvement Program database, composed of patient information and 30-day postoperative outcomes from >500 hospitals across the United States and targeted data files, which includes additional data on procedure-specific risk factors and outcomes in >100 of those participating hospitals. We analyzed patients undergoing hysterectomy for benign conditions from 2014 through 2015, identified by Current Procedural Terminology code. We excluded patients who had cancer, surgery by a nongynecology specialty, or missing uterine weight. Patients were compared with respect to 30-day postoperative complications and uterine weight, stratified by surgical approach. Bivariable tests and multivariable logistic regression were used for analysis. In all, 27,167 patients were analyzed. After adjusting for potential confounders, including medical and surgical variables, women with 500-g uteri were >30% more likely to have complications compared to women with uteri ≤100 g (adjusted odds ratio, 1.34; 95% confidence interval, 1.17-1.54; P < .0001), women with 750-g uteri were nearly 60% as likely (adjusted odds ratio, 1.58; 95% confidence interval, 1.37-1.82; P < .0001), and women with uteri ≥1000 g were >80% more likely (adjusted odds ratio, 1.85; 95% confidence interval, 1.55-2.21; P < .0001). The incidence of 30-day postsurgical complications was nearly double in the abdominal hysterectomy group (15%) compared to the laparoscopic group (8%). Additionally, for each stratum of uterine weight, abdominal hysterectomy had significantly higher odds of any complication compared to laparoscopic hysterectomy, even after adjusting for potential demographic, medical, and surgical confounders. For uteri <250 g, abdominal hysterectomy had twice the odds of any complication, compared to laparoscopic hysterectomy (adjusted odds ratio, 2.05; 95% confidence interval, 1.80-2.33), and among women with uteri between 250-500 g, abdominal hysterectomy was associated with an almost 80% increase in odds of any complication (adjusted odds ratio, 1.76; 95% confidence interval, 1.41-2.19). Even among women with uteri >500 g, abdominal hysterectomy was still associated with a >30% increased odds of any complication, compared to laparoscopic hysterectomy (adjusted odds ratio, 1.35; 95% confidence interval, 1.07-1.71). We found that while uterine weight was an independent risk factor for posthysterectomy complications, abdominal hysterectomy had higher odds of any complication, compared to laparoscopic hysterectomy, even for markedly enlarged uteri. Our study suggests that uterine weight alone is not an appropriate indication for abdominal hysterectomy. We also identified that it is safe to perform larger hysterectomies laparoscopically. Patients may benefit from referral to experienced surgeons who are able to offer laparoscopic hysterectomy even for markedly enlarged uteri.