Background: Cancer is the second most common cause of mortality in the United States. Cancer screening and prevention services have contributed to improved overall cancer survival rates in the past 40 years. Vulnerable populations (i.e., uninsured, low-income, and racial/ethnic minorities) are disproportionately affected by cancer, receive significantly fewer cancer prevention services, poorer healthcare, and subsequently lower survival rates than insured, white, non-Hispanic populations. The Affordable Care Act (ACA) aims to provide health insurance to all low-income citizens and legal residents, including an expansion of Medicaid eligibility for those earning ≤138% of federal poverty level. As of 2012, Medicaid was expanded in 32 states and the District of Columbia, while 18 states did not expand, creating a ‘natural experiment’ to assess the impact of Medicaid expansion on cancer prevention and care. Methods: We will use electronic health record data from up to 990 community health centers available up to 24-months before and at least one year after Medicaid expansion. Primary outcomes include health insurance and coverage status, and type of insurance. Additional outcomes include healthcare delivery, number and types of encounters, and receipt of cancer prevention and screening for all patients and preventive care and screening services for cancer survivors. Discussion: Cancer morbidity and mortality is greatly reduced through screening and prevention, but uninsured patients are much less likely than insured patients to receive these services as recommended. This natural policy experiment will provide valuable information about cancer-related healthcare services as the US tackles the distribution of healthcare resources and future health reform. Trial Registration: Clinicaltrails.gov identifier NCT02936609. Keywords: Cancer, Medicaid, Affordable Care Act, Natural experiment, Screening, Preventive services