Background The epidemiology of inflammatory bowel disease (IBD) is changing globally and there is disagreement between studies about the prevalence of relapse of ulcerative colitis (UC) as a type of IBD. Objectives The current study aimed to find out the incidence of relapses in patients with UC in Southern Iran. Patients and Methods In a prospective cohort study in a period of one year (from October 2012 to October 2013) 157 patients with UC who were in clinical remission for at least three months and were registered in the IBD registry of Shiraz University of Medical Sciences, Shiraz, Iran were enrolled. The sample size was calculated according to the formula to determine a ratio. Clinical relapse was described as deterioration of bowel movements, lower intestinal bleeding or worsening of abdominal pain and diarrhea leading to changes in previous treatment. Age and gender distribution and the frequency of relapse in a one-year follow-up were recorded. Results Among the 1273 registered patients with UC, 157 patients were enrolled in the survey by systematic sampling. Among patients, 48.7% were female and no significant difference was observed between the mean age of two gender groups (P = 0.70). Seventy-four patients, 48.1% (33 males and 41 females), relapsed during the 12-month follow-up period and the main medication of the 64 non-relapsing (80%) and 62 relapsing (83.8%) patients was mesalazin (P = 0.65). Conclusions Although, the reported incidence was almost equal to previous reports from other regions of the world, relapsed and non-relapsed UC patients received mesalazin as treatment without any significant differences.