PURPOSE: To compare the accuracy of polyp measurement at computed tomographic (CT) colonography by using two-dimensional (2D) multiplanar reformation (MPR) and three-dimensional (3D) endoluminal displays obtained both in a colon phantom and at clinical examinations. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval, and all patients provided signed informed consent, both of which allowed for additional retrospective evaluation. Two-dimensional and 3D CT colonography displays were generated from data obtained in an in vitro colon phantom that contained 10 6-13-mm synthetic polyps and from data obtained at in vivo clinical CT colonography examinations performed in 10 patients (five men, five women; mean age, 56.3 years) with proved polyps (size range, 7-25 mm). The reference standard for in vivo polyp size was optical colonoscopic measurement with a calibrated linear probe. Polyps were measured at CT colonography with 2D MPR and 3D endoluminal displays and electronic calipers by four radiologists who were unaware of the reference size measurements. The largest of the three 2D MPR measurements was considered the "optimized" 2D projection. Statistical analysis was performed with Wilcoxon signed rank, repeated-measures analysis of variance, and paired t testing. RESULTS: For the phantom, the mean errors (differences between actual polyp size and that measured at CT colonography) for 2D transverse, 2D coronal, and 3D endoluminal displays were 1.6 mm ± 0.8 (standard deviation), 1.4 mm ± 0.7, and 0.8 mm ± 0.5, respectively. For in vivo polyp measurements, the mean errors for 2D transverse, 2D coronal, 2D sagittal, and 3D displays were 4.4 mm ± 3.5, 3.8 mm ± 3.3, 4.6 mm ± 3.0, and 1.9 mm ± 1.6, respectively. The 2D measurements underestimated actual polyp sizes in all cases. The differences in mean errors between 2D MPR and 3D endoluminal measurements were significant (P < .05). When the optimized 2D view was considered for in vivo measurement, the mean error decreased to 3.0 mm ± 2.6 (P = .2). CONCLUSION: Linear polyp measurement on 3D endoluminal views was significantly more accurate than measurement on 2D transverse, coronal, or sagittal views, both in vitro and in vivo, for the CT colonography system evaluated. Use of the optimized 2D view substantially reduced 2D measurement error and may be valuable when used in conjunction with 3D measurement.