Background: An oral chemotherapy safety event prompted analysis of related workflows utilizing lean quality improvement methodology. This analysis identified high variation in prescription processing, lack of standardized safety checks, inefficient use of pharmacy time, and inadequate data collection. Our goal was to create an oral chemotherapy protocol that could ensure patients have the right oral chemotherapy agent, at the right dose, at the right time, with independent and efficient safety checks by nursing, pharmacy, and providers. Methods: Multidisciplinary teams participated in two kaizen workshops. utilizing lean methodology. Primary workshop objectives were (1) develop safety standards for oral chemotherapy similar to those for intravenous chemotherapy; (2) make workflows more efficient; and (3) have workflows that enable data collection and process control. The first workshop standardized oral chemotherapy prescription processing though a single workflow in the EMR. This enabled robust data collection and established a platform for safety interventions. The second workshop developed standardized safety checks for and integrated those into the EMR workflow. Given the rarity of serious safety events, a validation measurement was not feasible to track in 30-day PDCA cycles. Consequently, surrogate measures of utilization of the EMR prescribing algorithm and reduction of non-clinical pharmacy interventions were used to assess progress. Safety data were collected and correlated to surrogate outcomes for long-term impact assessment. Results: Interventions resulted in the following outcomes: 100% reduction in oral chemotherapy order defects reaching pharmacy; 97% improvement processing oral chemotherapy though a single EMR workflow; 23% reduction in oral chemotherapy processing time; In spite of a 51% increase in oral chemotherapy volume, no serious safety events have occurred in the last year. Conclusions: Comprehensive quality improvement in our oral chemotherapy process increased safety and efficiency while developing data collection systems for continuous improvement. Multidisciplinary workshops with key stakeholders using established lean methodology were critical to success.