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CT colonography (CTC) is a validated screening test for detection and prevention of colorectal cancer (CRC). In the United States, screening CTC has been covered for Medicare beneficiaries since 2025, elevating it to equal status with other reimbursed CRC screening tests and ending a 15-year policy stalemate. Screening CTC is a highly accurate examination with an immaculate safety record and equivalent sensitivity to colonoscopy for clinically significant polyps. Long-term observational CTC cohorts confirm safety for established polyp size thresholds in terms of test positivity and screening and surveillance intervals. Excellent technique with cathartic bowel preparation, stool tagging, and colonic distention is necessary for high-quality imaging and interpretation, particularly in detection of flat sessile serrated lesions (SSLs). Large SSLs and adenomatous polyps are the most relevant benign precursor lesions to CRC and are the main target of a primary prevention screening strategy. Only CTC and colonoscopy are sufficiently accurate for primary prevention, whereas stool-based and recently approved blood-based tests are limited to detection of cancer in a shorter screening window. CTC allows for selective polypectomy by risk-stratifying large polyps for removal, surveilling small polyps, and ignoring diminutive lesions. CTC is more efficient at identifying advanced neoplasia compared with a universal polypectomy strategy of colonoscopy only, which removes more pseudodisease and incurs excess risk of colonic perforation without benefit. Despite abundant evidence supporting CTC as an ideal screening test, it suffers from widespread and worsening underutilization due to barriers affecting radiology practice and physician support. Opportunistic screening and national trends in the CRC screening landscape will impact future uptake of CTC.