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Abstract Objectives We sought to determine if there is an association between preoperative risk factors as defined by the American Society of Anesthesiologists (ASA) physical status score and the route of hysterectomy for benign indications. Methods In this retrospective cohort study, the American College of Surgeons National Surgical Quality Improvement Project database was used to determine the route of hysterectomy, using Current Procedural Terminology codes, and associated ASA class. The analysis included abdominal, vaginal, total laparoscopic, and laparoscopic assisted vaginal routes of hysterectomy. Routes of hysterectomy were also grouped as either abdominal or minimally invasive for analysis. Multinomial logistic regression was used to model route of hysterectomy as a function of patient covariates, including ASA class, age, race and ethnicity, and body mass index. Results The analysis included 117,919 patients from the National Surgical Quality Improvement Project database. Patients with ASA classification of III or IV to V had significantly decreased odds of undergoing a minimally invasive approach for hysterectomy (odds ratio [OR], 0.81 [95% confidence interval (CI)], 0.77–0.85; and OR, 0.42 [95% CI, 0.37–0.48], respectively). Secondary outcome analysis revealed that a body mass index of more than 30 kg/m2 was associated with significantly lower odds of undergoing a minimally invasive hysterectomy (OR, 0.87; 95% CI, 0.85–0.89). With respect to race/ethnicity, all non-White groups had decreased odds of undergoing a hysterectomy via a minimally invasive approach. Age 75 years or older was correlated with an increased likelihood of minimally invasive hysterectomy (OR, 1.18; 95% CI, 1.10–1.26). Conclusions Patients with increased preoperative risk as defined by a high ASA classification are less likely to undergo a hysterectomy using a minimally invasive route for benign indications. [ABSTRACT FROM AUTHOR]