Background: Use of oral chemotherapy is expanding and offers advantages but introduces unique safety challenges. ASCO and ONS addressed these issues with inclusion of oral chemotherapy in published chemotherapy administration safety standards. Methods: The updated ASCO/ONS standards offered a framework for the University of Wisconsin Carbone Cancer Center to evaluate and improve our practice with the goal of full compliance with these standards. Gap analysis revealed noncompliance with five and partial compliance with eleven standards. We divided areas for improvement into three foci: patient education, workflow, and information technology. Multidisciplinary groups addressed each area generating twenty-five recommendations. Important changes included: defining chemotherapy, standardization of patient and caregiver education, mandated use of standardized electronic order sets incorporating safety checks, and standardizing dose modification documentation. The revised electronic process allows for prospective order review of all oral chemotherapy by pharmacists and supports automated processes for assessing adherence and toxicities utilizing a library of scripted drug specific materials. Results: Prior to implementation of new processes we estimated that only 39% of our oral chemotherapy was delivered with potential demonstrable compliance with ASCO/ONS standards. Audit of oral chemotherapy orders from February to July 2015 now shows compliance with use of electronic chemotherapy plans in 244/251 (97.5%) of cases. Prospective pharmacist order review resulted in one or more interventions in 24% of these cases.Identification of patients to receive adherence and toxicity monitoring calls is 100%. Conclusions: Closure of significant gaps between institutional practice and published standards was accomplished for our oral chemotherapy practice. Key elements of success included: multidisciplinary approach, defining chemotherapy, leveraging our electronic health record with mandated use of standardized order sets, and standardization of clinical and educational processes. We are disseminating this approach across our regional network and we believe our tools are broadly applicable.