<h3>Purpose/Objective(s)</h3> Prior data have linked Medicaid expansions under the Affordable Care Act with improved insurance coverage among patients with cancer, earlier stages at diagnosis, and prolonged survival. Decreased cancer mortality rates were observed in connection with the limited early Medicaid expansions in 2010-2011, but changes associated with the more comprehensive and more recent Medicaid expansions starting in 2014 are not clear. We sought to test our hypothesis that Medicaid expansion was associated with decreased cancer mortality rates. <h3>Materials/Methods</h3> Data for cancer deaths among 20–64-year-old individuals from 2004-2018 were obtained from the National Center for Health Statistics. We obtained annual state-level cancer mortality rates covering all 50 U.S. states for deaths for all cancers combined and for deaths due to breast, cervical, colorectal, liver, lung, pancreatic, and prostate cancers, stratified by age group. State-level demographic data summarizing, age, employment, education, poverty, race/ethnicity, insurance, smoking, and obesity were also obtained and linked with the mortality data. We implemented a difference-in-differences analysis utilizing generalized estimating equations with state-level clustering to compare changes in mortality rates after 2014 between Medicaid expansion and non-expansion states. Models were adjusted for age, year, early (2010-2011) Medicaid expansion effects, and the aforementioned state-level demographic covariates. The common or parallel trends assumption was evaluated by examining for differential temporal trends in mortality rates between state groups and was satisfied for all analyses. Sensitivity analyses with interrupted time series analyses comparing trends in state groups were performed. <h3>Results</h3> Mortality rates for all cancers combined decreased from 92.2 to 85.5 per 100,000 in Medicaid expansion states compared to 98.4 to 93.5 per 100,000 in non-expansion states after 2014. In adjusted difference-in-differences analyses for all cancers combined, cancer mortality rates decreased after Medicaid expansion in expansion relative to non-expansion states (OR: 0.982, 95% CI = 0.965-0.999, p=.038), translating to 5174 cancer deaths that were averted in Medicaid expansion states in the post-expansion period. Expansion-associated reductions in mortality were also observed for breast (OR: 0.970, 95% CI = 0.947-0.993, p = 0.012), liver (OR: 0.939, 95% CI = 0.894-0.986, p = 0.011), and pancreatic cancers (OR: 0.968, 95% CI = 0.942-0.995, p = 0.019). Sensitivity analyses yielded similar results. <h3>Conclusion</h3> These data are the first to show statistically significant associations between state Medicaid expansions after 2014 and decreased overall cancer mortality rates. We observed expansion-associated reductions for all cancers combined and for breast, liver, and pancreatic cancers. Further advocacy efforts focusing on the 12 states that have not yet adopted Medicaid expansion may further reduce cancer mortality.