CT colonography without bowel preparation is a safer and bettertolerated alternative to full laxation protocols, but comparative sensitivity and specificity are potentially reduced. Uptake of 18 F-FDG by colonic neoplasia is well described, and combining PET with nonlaxative CT colonography could improve accuracy. The purpose was to prospectively test the technical feasibility and acceptability of combined nonlaxative PET/CT colonography in patients at higher risk of colorectal neoplasia and to provide pilot data on diagnostic performance. Methods: Fifty-six patients (median age, 64 y; 30 women) at high risk of colonic neoplasia underwent nonlaxative PET/CT colonography with barium fecal tagging within 2 wk of scheduled colonoscopy. Colonic segmental distension was graded 1 (poor) to 3 (good). A radiologist, experienced in CT colonography, and nuclear medicine physician in consensus analyzed the datasets. The diagnostic performance for standalone CT colonography and combined PET/CT colonography was compared with the reference colonoscopy. Patient experience for 25 items (each scored from 1 to 7) pertaining to satisfaction, worry, and physical discomfort was canvassed after both PET/CT colonography and colonoscopy. Results: Distension was good in 298 of 334 segments (89%; 95% confidence interval [CI], 85%292%). Patients experienced more physical discomfort during colonoscopy (median, 4; interquartile range [IQR], 2-7) than during PET/CT colonography (median, 5; IQR, 3-7; P 5 0.03) and were more willing to undergo PET/CT colonography again (36/43 [84%; 95% CI, 73%295%] vs. 31/43 [72%; 95% CI, 59%286%]; P 5 0.001). Twenty-one patients had 54 polyps according to colonoscopy (10 with at least 1 polyp $6 mm and 8 with at least 1 polyp $10 mm). Of 14 polyps 6 mm or greater, 12 (86%; 95% CI, 67%2100%) were 18 F-FDG-avid, including all those 10 mm or greater (mean standardized uptake value, 10.1). CT colonography sensitivity for polyps 6 mm or larger was 92.9% (95% CI, 79.4%2100%) and was not improved by the addition of PET. However, combined PET/CT colonography review improved per-patient positive predictive value for a polyp 10 mm or greater from 73% (95% CI, 39-92) to 100% (95% CI, 60-100). Conclusion: In this feasibility study, simultaneous PET acquisition during nonlaxative CT colonography is technically feasible, is well tolerated, and potentially improves specificity.