Abstract Background Less postoperative pain is typically associated with a minimally invasive hysterectomy compared to a laparotomy approach but poor pain control can still be an issues. Multiple guidelines exist for managing postoperative pain yet most are not specialty-specific and are based on procedures bearing little relevance to a minimally invasive hysterectomy. Objective To determine if there is enough quality evidence within the benign gynecology literature to make non-opioid pain control recommendations for women undergoing a benign minimally invasive hysterectomy. Study Design We queried PubMed, ClinicalTrials.gov and Cochrane databases using MeSH terms: “postoperative pain,” “perioperative pain,” “postoperative analgesia,” “pain management,” “pain control,” “minimally invasive gynecologic surgery” and “hysterectomy”. A manual examination of references from identified studies was also performed. All PubMed published studies involving minimally invasive hysterectomies through November 9, 2016 were included. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were restricted to benign minimally invasive hysterectomies evaluating non-opioid pharmacologic therapies. Primary outcomes included amount of postoperative analgesics consumed and postoperative pain scores. Two reviewers independently completed an in-depth evaluation of each study for characteristics and results using an Excel database according to inclusion/exclusion criteria. A risk assessment was performed and a quality rating assigned using the Cochrane Collaboration’s Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results Initially 1,155 studies were identified, 24 met all inclusion criteria. Based on limited data of varying quality, intravenous (IV) acetaminophen, anticonvulsants and dexamethasone demonstrate opioid-sparing benefits while ketorolac shows mixed results in laparoscopic hysterectomies. Paracervical blocks provide pain-reducing benefits in vaginal hysterectomies. Conclusions Convincing conclusions are difficult to draw because of the heterogeneous and contradictory nature of the literature. There is a clear need for more high-quality research evaluating each medication type for post-hysterectomy pain control.