Background and Aims: The disease course of microscopic colitis [MC], encompassing collagenous colitis [CC] and lymphocytic colitis [LC], is not well known. In a Danish nationwide cohort, we evaluated the disease activity patterns as well as the risk of colorectal cancer [CRC] and mortality based on disease severity. Methods: All incident MC patients [n = 14 302] with a recorded diagnosis of CC [n = 8437] or LC [n = 5865] in the Danish Pathology Register, entered between 2001 and 2016, were matched to 10 reference individuals [n = 142 481]. Incident cases of CRC after the index date were captured from the Danish Cancer Registry. Mortality data were ascertained from the Danish Registry of Causes of Death, and information about treatment was obtained from the Danish National Prescription Registry. The risk of CRC and mortality analyses were investigated by Cox regression and Kaplan-Meier estimates. Results: We identified a self-limiting or transient disease course in 70.6% of LC patients and in 59.9% of CC patients, p<0.001. Less than 5% of MC patients experienced a budesonide-refractory disease course and were treated with immunomodulators or biologic treatment. A total of 2926 [20.5%] MC patients and 24 632 [17.3%] reference individuals died during the study period. MC patients with a severe disease had a relative risk [RR] of mortality of 1.41 (95% confidence interval [CI]: 1.32-1.50) compared with reference individuals. Only 90 MC patients were diagnosed with CRC during follow-up, corresponding to an RR of 0.48 [95% CI: 0.39-0.60]. Conclusions: A majority of MC patients experience an indolent disease course with a lower risk of developing CRC compared with the background population.