ABSTRACT: Importance:Despite advances in cancer treatment and cancer-related outcomes, disparities in cancer mortality remain. Lower rates of cancer prevention screening and consequent delays in diagnosis may exacerbate these disparities. Better understanding of the association between area-level social determinants of health and cancer screening may be helpful to increase screening rates. Objective:To examine the association between area deprivation, rurality, and screening for breast, cervical, and colorectal cancer in patients from an integrated health care delivery system in 3 US Midwest states (Minnesota, Iowa, and Wisconsin). Design, Setting, and Participants:In this cross-sectional study of adults receiving primary care at 75 primary care practices in Minnesota, Iowa, and Wisconsin, rates of recommended breast, cervical, and colorectal cancer screening completion were ascertained using electronic health records between July 1, 2016, and June 30, 2017. The area deprivation index (ADI) is a composite measure of social determinants of health composed of 17 US Census indicators and was calculated for all census block groups in Minnesota, Iowa, and Wisconsin (11?230 census block groups). Rurality was defined at the zip code level. Using multivariable logistic regression, this study examined the association between the ADI, rurality, and completion of cancer screening after adjusting for age, Charlson Comorbidity Index, race, and sex (for colorectal cancer only). Main Outcomes and Measures:Completion of recommended breast, cervical, and colorectal cancer screening. Results:The study cohorts were composed of 78?302 patients eligible for breast cancer screening (mean [SD] age, 61.8 [7.1] years), 126?731 patients eligible for cervical cancer screening (mean [SD] age, 42.6 [13.2] years), and 145?550 patients eligible for colorectal cancer screening (mean [SD] age, 62.4 [7.0] years; 52.9% [77?048 of 145?550] female). The odds of completing recommended screening were decreased for individuals living in the most deprived (highest ADI) census block group quintile compared with the least deprived (lowest ADI) quintile: the odds ratios were 0.51 (95% CI, 0.46-0.57) for breast cancer, 0.58 (95% CI, 0.54-0.62) for cervical cancer, and 0.57 (95% CI, 0.53-0.61) for colorectal cancer. Individuals living in rural areas compared with urban areas also had lower rates of cancer screening: the odds ratios were 0.76 (95% CI, 0.72-0.79) for breast cancer, 0.81 (95% CI, 0.79-0.83) for cervical cancer, and 0.93 (95% CI, 0.91-0.96) for colorectal cancer. Conclusions and Relevance:Individuals living in areas of greater deprivation and rurality had lower rates of recommended cancer screening, signaling the need for effective intervention strategies that may include improved community partnerships and patient engagement to enhance access to screening in highest-risk populations.