To evaluate the effect of experience on the accuracy rate of computed tomography colonography (CTC) interpretation and patient preferences/satisfaction for CTC and colonoscopy. A prospective, non-randomized, observational study performed in a single, tertiary care center involving 90 adults who underwent CTC followed by colonoscopy on the same day. CTC was interpreted by an abdominal imaging radiologist and then a colonoscopy was performed utilizing segmental un-blinding and re-examination as required. A radiology resident and two gastroenterology (GI) fellows blinded to the results also interpreted the CTC datasets independently. Accuracy rates and trend changes were determined for each reader to assess for a learning curve. Among 90 patients (57% male) aged 55 ± 8.9 years, 39 polyps ≥ 6 mm were detected in 20 patients and 13 polyps > 9 mm in 10 patients. Accuracy rates were 88.9% (≥ 6 mm) and 93.3% (> 9 mm) for the GI Radiologist, 89.8% (≥ 6 mm) and 98.9% (> 9 mm) for the Radiology Resident and 86.7% and 95.6% (≥ 6 mm) and 87.8% and 94.4% (> 9 mm) for each of the GI fellows respectively. The reader's accuracy rate did not change significantly with the percentage change rate ranging between -1.7 to 0.9 (P = 0.12 to 0.56). Patients considered colonoscopy more satisfactory than CTC (30% vs 4%, P < 0.0001), they felt less anxiety during colonoscopy (36% vs 7%, P < 0.0001), they experienced less pain or discomfort during colonoscopy compared to CTC (69% vs 4%, P < 0.0001) and colonoscopy was preferred by 77% of the participants as a repeat screening test for the future. No statistically significant learning curve was identified in CTC interpretation suggesting that further study is required to identify the necessary training to adequately interpret CTC scans.