INTRODUCTION: Medication nonadherence is a prevalent issue in the oncology population and can be costly on the healthcare system while leading to worsened outcomes, including increased mortality. One intervention that has been shown to help promote medication adherence to oral therapies for chronic conditions is blister-packaging. However, no literature is available assessing the potential impact of blister-packaging in oncology. Therefore, we aimed to quantify the impact of blister-packaging oral oncolytics on medication adherence and healthcare costs. METHODS: An economic model was designed to assess the potential impact of blister-packaging oral oncolytics for chronic lymphocytic leukemia (CLL) patients in the U.S. The model took the perspective of the U.S. healthcare system and assessed newly diagnosed CLL cases initiating therapy, utilizing a one-year time horizon. The intervention of interest was blister-packaging oral therapies in the treatment of CLL, while the model evaluated the impact of this intervention on healthcare costs through improved patient adherence based on peer-reviewed literature. RESULTS: This analysis consisted of 20,700 newly diagnosed patients with CLL initiating therapy. Initiating blister-packed oral therapies saw adherence increase by 1004 patients from 12,979 patients (62.7%) to 13,983 patients (67.5%). While an increase in pharmacy costs by 1,589,670 (+47.95 per-patient per-month (PPPM)) was seen for the population, medical costs decreased by 2,285,847 (-31.26 PPPM). Overall, this led to a net reduction in total healthcare costs of 0,696,177 (-3.32 PPPM). CONCLUSIONS: Blister-packaging oral oncology drugs in CLL has the potential to reduce total healthcare expenditures by increasing medication adherence. Future studies are needed to evaluate the direct effects of blister-packaging oral oncolytics on clinical, healthcare resource utilization, and financial outcomes.