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Background: The aim of our study was to compare colon capsule endoscopy (CCE) with standard colonoscopy (SC) in the assessment of mucosal disease activity and localization of inflammatory colonic mucosa in patients with known ulcerative colitis (UC)., Methods: Thirteen symptomatic patients (8 males, 5 females, mean age 38.5 ± 12.0 years) with known UC (mean duration of colitis: 9.7 ± 8.1 years) and indication for endoscopy due to suspected disease activity were included. All patients underwent CCE (first generation capsule, Given Imaging Ltd., Yokneam, Israel) on day 1 followed by SC on day 2 in a single center non-randomized, non-placebo-controlled diagnostic study (NCT00837304). SC and CCE were video recorded, and analysis was independently performed by 6 experienced endoscopists. The modified Rachmilewitz score was calculated, and Wilcoxon signed-rank test was used for analysis. Difference in recognition of disease activity by the endoscopists was assessed by application of the Kruskal-Wallis test., Results: Assessment of disease activity revealed a significantly higher Rachmilewitz score of 7.3 ± 2.9 in the SC group compared to 4.8 ± 3.4 in the CCE group. Significantly, more detection of vessel vulnerability, granulated mucosa and mucosal damage was seen by SC. Disease extension was underestimated by CCE compared to SC. Disease activity assessment by means of SC or CCE did not differ statistically between the investigators (p = 0.26 and p = 0.1, respectively). After CCE, the capsule egestion rate was 77 %. The overall acceptance of both procedures was similar., Conclusion: Considering the significantly different assessment of disease activity and significantly more appropriate assignment of the horizontal spread of inflammation by SC versus CCE, we recommend the preferential use of SC in the assessment of inflammation in UC patients.