Background: The Affordable Care Act (ACA) Medicaid Expansion (ME) resulted in increased use of Medicaid insurance nationwide. However, the impact of the ACA ME on access to clinical trials has not been examined. Methods: We examined the number and proportion of patients insured by Medicaid at enrollment over time using data from the SWOG Cancer Research Network. We examined all patients 18-64 years old enrolled to treatment trials between April 1, 1992 to February 28, 2020 using Medicaid vs. private insurance. Interrupted time-series analysis was used; first implementation of the ACA ME (in 2014) was the independent exposure variable. Segmented logistic regression was used to estimate the difference between actual enrollment of patients using Medicaid to the expected rate had the ACA ME not been implemented. To account for secular trends related to economic conditions, we adjusted for the monthly unemployment rate using data from the Bureau of Labor Statistics. Indicator variables to reflect administrative differences in Medicaid by presidential administration were included. Results: In total, 47,042 patients age < 65 years were analyzed, including 31,565 (67.1%) females, 18,987 (40.4%) age < 50 years, and 4,709 (10.0%) with Medicaid coverage. Overall, a 20% (OR = 1.20, 95% CI, 1.11-1.30, p <.001) increase per year in the odds of patients using Medicaid was detected following the ACA ME. Based on pre-ACA patterns, the proportion of patients using Medicaid decreased during periods of economic growth and low unemployment; thus, the model-based estimate of the proportion of patients with Medicaid insurance had the ACA ME not occurred was only 7.4% (95% CI, 4.8%-9.5%) at the end of the study period (February 2020), when national unemployment was low (3.5%). In contrast, the actual rate was 20.8% (95% CI, 17.1%-25.0%). Patterns were consistent by age but not by sex, with a stronger 29% (OR = 1.29, 95% CI, 1.17-1.42, p <.001) annual increase in the proportion of Medicaid use for female patients compared to only 7% (OR = 1.07, 95% CI, 0.94-1.23, p =.26) for males. The increase per year of Medicaid use for patients from states that implemented the ME in 2014 or 2015 was 27% (OR = 1.27, 95% CI, 1.16-1.41, p <.001) compared to 7% for patients from other states (OR = 1.07, 95% CI, 0.94-1.22, p =.28). Conclusions: The implementation of the ACA ME was associated with nearly a threefold increase (20.8% vs. 7.4%) in the proportion of patients using Medicaid in cancer clinical trials by early 2020. Improved access to clinical trials for more vulnerable patients is critical for improving confidence that trial findings apply to the general cancer population. These findings suggest that the recently enacted Cancer Treatment Act – which mandates that state Medicaid programs cover the routine care costs of clinical trial participation – may continue to improve access to clinical trials for those with Medicaid insurance.