BACKGROUND: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment. METHOD: The number of US childhood patients with cancer diagnosed <20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates. Observed-to-expected ratios and corresponding 95% confidence intervals (CI) were estimated across sex, race, diagnosis age, calendar year, and cancer diagnosis groups. Multivariable linear regression models were generated to evaluate the association between open COG phase 3 therapeutic trials and CCRN enrollment rates. RESULT: The 43,110 cases enrolled in CCRN represented 36% of the expected childhood cancers diagnosed from 2008 to 2015 (N = 120,118). CCRN enrollment ratios [95% CI] were highest among males (0.38 [95% CI, 0.37-0.38]), non-Hispanics (0.35 [95% CI, 0.35-0.36]), and those diagnosed from 1 to 4 years of age (0.50 [95% CI, 0.50-51]). Enrollment ratios varied by diagnosis group, with leukemia, myeloproliferative diseases, myelodysplastic diseases (0.55 [95% CI, 0.54-0.55]), and renal tumors (0.55 [95% CI, 0.53-0.58]) having the highest enrollment. After adjusting for year of diagnosis and cancer diagnosis, there was a 3.1% [95% CI, 0.6-5.6%] increase in CCRN enrollment during windows of open COG therapeutic trials. CONCLUSIONS: Despite enrolling only 36% of newly diagnosed cases, CCRN remains a valuable resource for investigators conducting childhood cancer etiology and survivorship research. The results of this study may inform efforts to improve enrollment on current and future COG nontherapeutic registry protocols.