Clinical research nurses and non-licensed study coordinators observed variation in procedures for reconciliation and disposal of oral investigational medications across the institution. An academic medical center implemented a quality improvement project to standardize the process of reconciliation and disposal of oral investigational medications. An interprofessional collaborative workgroup was formed, which led to multiple interventions to standardize practice, including revision of three policies and procedures, redesign of specific work areas to establish drug-counting rooms, review of personal protective equipment requirements, revision of educational training, and regular cleaning of potentially contaminated workstations.