Colonoscopy and polypectomy effectively reduce the incidence and mortality of colorectal cancer, but some patients present with fully developed cancers within 1-4 yr of a colonoscopy that apparently cleared the colon of neoplasia. These events may result in medical-legal action against colonoscopists, generally based on an assumption of negligent technical performance of the procedure. Alternative explanations for the development of interval cancers include variable growth rates of colorectal cancers, the inherent miss rate of the procedure even when optimal examination techniques are used, and the possibility of flat lesions that are not readily detected by standard colonoscopic techniques. This paper discusses issues relevant to reduction of medical-legal risks associated with interval cancers after clearing colonoscopy. These issues include informed consent, documentation of cecal intubation, appropriate description of preparation, documentation of examination time and technique, and attention to potential atypical neoplasms.