Objective. As the lifespan of patients with cystic fibrosis (CF) increases, concerns regarding the occurrence of bowel cancer have arisen. However, previous cohort studies have yielded contradictory results as to the risk of colorectal cancer (CRC) in the CF population. The aim of this study was to determine whether CF is associated with an increased risk of colorectal neoplasia. Methods. We performed a matched case-control study at a statewide CF center. Cases were adult CF patients undergoing colonoscopy in a 5-year period from 2007 to 2012. Controls were matched in a 2:1 ratio for age, gender, and colonoscopy indication. Results. A total of 50 patients with CF who underwent colonoscopy were identified. Among CF patients, there were 5 (10 ) cases with CRC, 1 (2 ) with ileal adenocarcinoma, 13 (26 ) with adenomas, and 16(32 ) with advanced adenomas. In contrast, there was 1 (1 ) case with CRC, 11 (11 ) with adenomas, and 6 (6 ) with advanced adenomas identified among controls. Compared to controls, CF was associated with a 10-fold increased risk of CRC (odds ratio [OR] = 10.0, 95 confidence interval [CI]: 1.2-85.6; p = 0.03), threefold increased risk of adenomas (OR = 3.34, 95 CI: 1.23-9.08; p = 0.018], and sevenfold increased risk of advanced adenomas (OR = 6.95, 95 CI: 2.30-21.01; p = 0.001). Moreover, the quality of bowel preparation was significantly worse in CF patients with a fourfold (p = 0.01) increased likelihood of a poor preparation. Conclusions. Our data suggest that CF patients are at significantly increased risk of CRC compared to age, sex, and colonoscopy-indication matched controls. Consideration should be given to the introduction of a CRC surveillance program in the CF population.