We investigated the prevalence of amebiasis in patients with ulcerative colitis residing in two geographical regions with different socioeconomic status and climatic conditions, and its effect on the age of onset, duration, localization, and activity of disease. Ninety patients from a high socioeconomic location (group I) and 28 cases from a low socioeconomic location (group II) were enrolled. Median age at disease onset was significantly higher in group I compared with in group II. Prevalence of amebiasis in group I was significantly lower than in group II. A considerably number of patients with amebiasis in group I had a history of travel to the cities with a lower socioeconomic level, mainly located in the east of Turkey. There was a strong relationship between presence of amebiasis and history of travel to eastern parts of Turkey among residents from the northwestern part of Turkey. Median age and age at time of diagnosis were significantly lower in patients with amebiasis compared with those without infection. In patients with mild disease activity, prevalence of amebiasis was significantly lower compared with those with moderate or severe disease activity. In conclusion, prevalence of amebiasis was markedly higher in the southeast compared to the northwest of Turkey. Travel to regions with low socioeconomic status may be considered a risk factor for amebiasis in patients with ulcerative colitis. Amebiasis enhances disease activity in ulcerative colitis.