Background: Multiple sources have reported on widespread abuse of opioid pain medications among Americans. For many patients, the first encounter with these addictive substances happens when they are prescribed opioids for acute pain management after surgery. Unfortunately, 6% of opioid-naïve patients become newly addicted to opioid medications after surgery. As a high-volume surgical department, we aimed to reduce our reliance on opioid medications to manage post-operative pain by 50% from a baseline morphine equivalent daily dose (MEDD) of 95.1 to a target of 47.5 MEDD. Methods: We retrospectively reviewed daily opioid use, pain scores, and anxiety scores for inpatients recovering from surgery for urologic cancers at our institution over 4 months. We generated process maps, Ishikawa diagrams, and Pareto charts to identify causes contributing to excess opioid use. We designed opioid-sparing pain regimens (using varying combinations of acetaminophen, ketorolac, gabapentin, and local anesthetic) and we identified key drivers required to reliably decrease excess opioid use. Initial interventions were aimed at educating providers and nurses on availability and efficacy of non-opioid medications and later interventions sought to facilitate adoption of the novel pathways. Results: Over the course of this QI project involving 443 patients, the median opioid use per patient decreased 46% from 95.1 to 51.5 MEDD. This reduction in opioid requirements after implementation was successfully achieved across multiple surgery types ranging from robotic prostatectomy (55.1 MEDD) to open radical cystectomy (50.6 MEDD). There was no increase in 24- or 48-hour post-operative pain score associated with use of opioid-minimizing pathways (3.03 vs. 3.04 and 2.92 vs. 2.96, respectively; p > 0.05 for both). Similarly, there was no change in anxiety score at 24- or 48-hours after surgery (0.15 vs. 0.12 and 0.48 vs. 0.30, respectively; p > 0.05 for both). Conclusions: We decreased opioid use after surgery by 46% without compromising pain control. In the nationwide effort to combat the opioid epidemic, health care providers can play a pivotal role as gatekeepers by decreasing reliance on opioids in the post-operative period.