Background Colorectal cancer represents a significant cause of morbidity and mortality, particularly in Appalachia where high mortality from colorectal cancer is more prevalent. Adherence to treatment guidelines leads to improved survival. This paper examines determinants of guideline concordance for colorectal cancer. Methods Colorectal cancer patients diagnosed in 2006‐2008 from 4 cancer registries (Kentucky, Ohio, Pennsylvania, and North Carolina) were linked to Medicare claims (2005‐2009). Final sample size after exclusions was 2,932 stage I‐III colon, and 184 stage III rectal cancer patients. The 3 measures of guideline concordance include adjuvant chemotherapy (stage III colon cancer, <80 years), ≥12 lymph nodes assessed (resected stage I‐III colon cancer), and radiation therapy (stage III rectal cancer, <80 years). Bivariate and multivariate analyses with clinical, sociodemographic, and service provider covariates were estimated for each of the measures. Results Rates of chemotherapy, lymph node assessment, and radiation were 62.9%, 66.3%, and 56.0%, respectively. Older patients had lower rates of chemotherapy and radiation. Five comorbidities were significantly associated with lower concordance in the bivariate analyses: myocardial infarction, congestive heart failure, respiratory diseases, dementia with chemotherapy, and diabetes with adequate lymph node assessment. Patients treated by hospitals with no Commission on Cancer (COC) designation or lower surgical volumes had lower odds of adequate lymph node assessment. Conclusions Clinical, sociodemographic, and service provider characteristics are significant determinants of the variation in guideline concordance rates of 3 colorectal cancer measures.