The authors prospectively evaluated the implementation of a prespecified protocol to eliminate post-discharge opioid prescription after major urologic cancer surgery at a single center among a predominantly opioid naïve population. The intervention included both provider and patient education along with a standardized regimen for non-opioid analgesia during the inpatient stay and after discharge. Use of a standardized protocol nearly eliminated opioid prescriptions after major urologic cancer surgery without adversely impacting patient reported pain control and satisfaction, unplanned visits, and complications.