Few data are available about the clinical course of severe colonic Crohns disease (CD). The aim of this study is to describe the clinical course of severe Crohns colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohns colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohns Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohns colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of colectomy in the cohort of patients with severe Crohns colitis was greater than that of the cohort of patients with severe UC, but this figure is not supported by a different clinical response to steroid therapy or rescue therapy with biologics. The clinical course of severe Crohns colitis requires to be clarified by prospective studies that include a larger number of patients in this subgroup of disease.