The clinical relevance and in-vivo growth rates of small (6-9 mm) colorectal polyps are not well established. We aimed to assess the behaviour of such polyps with CT colonography assessments. In this longitudinal study, we enrolled asymptomatic adults undergoing routine colorectal cancer screening with CT colonography at two medical centres in the USA. Experienced investigators (PJP, DHK, JLH) measured volumes and maximum linear sizes of polyps in vivo with CT colonography scans at baseline and surveillance follow-up. We defined progression, stability, and regression on the basis of a 20% volumetric change per year from baseline (20% or more growth classed as progression, 20% growth to -20% reduction classed as stable, and -20% or more reduction classed as regression). We compared findings with histological subgroups confirmed after colonoscopy when indicated. This study is registered with ClinicalTrials.gov, number NCT00204867. Between April, 2004, and June, 2012, we screened 22,006 asymptomatic adults and included 243 adults (mean age 57·4 years [SD 7·1] and median age 56 years [IQR 52-61]; 106 [37%] women), with 306 small colorectal polyps. The mean surveillance interval was 2·3 years (SD 1·4; range 1-7 years; median 2·0 years [IQR 1·1-2·3]). 68 (22%) of 306 polyps progressed, 153 (50%) were stable, and 85 (28%) regressed, including an apparent resolution in 32 (10%) polyps. We established immediate histology in 131 lesions on colonoscopy after final CT colonography. 21 (91%) of 23 proven advanced adenomas progressed, compared with 31 (37%) of 84 proven non-advanced adenomas, and 15 (8%) of 198 other lesions (p<0·0001). The odds ratio for a growing polyp at CT colonography surveillance to become an advanced adenoma was 15·6 (95% CI 7·6-31·7) compared with 6-9 mm polyps detected and removed at initial CT colonography screening (without surveillance). Mean polyp volume change was a 77% increase per year for 23 proven advanced adenomas and a 16% increase per year for 84 proven non-advanced adenomas, but a 13% decrease per year for all proven non-neoplastic or unresected polyps (p<0·0001). An absolute polyp volume of more than 180 mm(3) at surveillance CT colonography identified proven advanced neoplasia (including one delayed cancer) with a sensitivity of 92% (22 of 24 polyps), specificity of 94% (266 of 282 polyps), positive-predictive value of 58% (22 of 38 polyps), and negative-predictive value of 99% (266 of 268 polyps). Only 16 (6%) of the 6-9 mm polyps exceeded 10 mm at follow-up. Volumetric growth assessment of small colorectal polyps could be a useful biomarker for determination of clinical importance. Advanced adenomas show more rapid growth than non-advanced adenomas, whereas most other small polyps remain stable or regress. Our findings might allow for less invasive surveillance strategies, reserving polypectomy for lesions that show substantial growth. Further research is needed to provide more information regarding the ultimate fate of unresected small polyps without significant growth. US National Institutes of Health, National Cancer Institute.