Background: The conscientious prescribing of antiemetics by chemotherapy-induced nausea and vomiting (CINV) risk was highlighted in the American Society of Clinical Oncology (ASCO) “Choosing Wisely” recommendations. The pharmacologic properties of medical marijuana (MMJ) and increased availability through legislation may allow for decreased incidence of CINV, however, little is known about the effects of MMJ legislation on the use of antiemetics. The objective is thus to assess the association between MMJ cardholder status in Arkansas and antiemetic overuse among cancer patients. Methods: A retrospective cohort was derived from the linked Arkansas All Payers Claims Database (APCD; 2013-2020) and MMJ card holder data (2013-2019). The cohort of interest consisted of individuals aged 18 and older with a chemotherapy claim in outpatient setting within 12 months of a cancer diagnosis. Exposed individuals had access to MMJ through an MMJ card. The primary outcome of interest was antiemetic overuse, as characterized by the ASCO recommendation. Antiemetic use was identified using prescription claims and coded as present if an antiemetic prescription was identified between two weeks prior to two days following chemotherapy receipt. Logistic regression, adjusted for baseline demographic and prescription characteristics, were used to calculate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) of experiencing antiemetic overuse. Results: Within Arkansas, 22,139 individuals without a MMJ card received 167,084 chemotherapy cycles and 161 individuals with a MMJ card received 2,775 chemotherapy cycles. Antiemetic overuse was identified in 6.59% versus 5.87% of chemotherapy cycles among non-MMJ cardholders and MMJ cardholders respectively. The calculated aOR of antiemetic overuse among individuals with a MMJ card was .671 (95%CI:.567-.794) when compared to individuals without a MMJ card. Conclusions: The findings indicate that MMJ cardholders are significantly less likely to experience antiemetic overuse than individuals without MMJ cards. Increased awareness of ASCO’s recommendation and further investigation into the use, effectiveness, and safety of cannabis for the use of CINV mitigation is needed to inform patient and provider decision-making.