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Objective Colon capsule endoscopy (CCE) is a new endoscopic technique that is minimally invasive and allows evaluation of the colon mucosa without pain, sedation, and gas insufflation. To date, few studies have investigated the use of CCE in patients with ulcerative colitis (UC). This study compares the ability of CCE and a conventional colonoscopy to assess mucosal disease activity and the extent of inflammatory mucosa in patients with UC. Methods Forty-two patients (27 men, mean age 48.5 years) with known UC and indication for colonoscopy were enrolled in this single-blind, prospective study. All patients underwent CCE, followed by a colonoscopy. The activity and extent of the disease was assessed using Mayo scores and Montreal scores, respectively. Results There was a good correlation between CCE and colonoscopy in disease severity (κ=0.79; 95% confidence interval: 0.62-0.96) and extent of inflammation (κ=0.71; 95% confidence interval: 0.52-0.90) observed. The ability of CCE to assess a broad segment of distal ileum led to a change in the diagnosis of UC to ileocolonic Crohn's disease in three patients. Bowel preparation was considered adequate in 80% of the patients and no serious adverse events related to the CCE procedure or bowel preparation were reported. Conclusion CCE is a safe and useful method for the evaluation of patients with UC. The ability of CCE to assess distal ileum provides an advantage to colonoscopy as CCE can identify patients who have been incorrectly diagnosed with UC, resulting in a change in their diagnosis to Crohn's disease.