Aminosalicylates are effective in inducing remission and are also useful in preventing relapse of ulcerative colitis (UC); however, previous studies have reported a 30%-45% rate of nonadherence to prescribed medication among UC patients. Enumerating and conceptualizing the difficulties in taking aminosalicylates enable us to assess and support patients more effectively. The aim of this study was to investigate the difficulties in taking aminosalicylates among Japanese UC patients and explore factors related to these difficulties. Outpatients with UC (n = 242) completed a questionnaire supported by a semistructured interview on the basis of a literature review. Twelve items about difficulties in taking aminosalicylates were processed by factor analysis and the related factors regarding difficulties were analyzed. The following three independent domains were identified: Domain 1: diminished sense of priority for medication; Domain 2: concern about side effects; and Domain 3: burden of taking the prescribed drug. Factors related to the difficulties in taking aminosalicylates included the disease state, psychosocial factors, and demographic characteristic variables. On the basis of the results, we recommend the creation and validation of a program aimed at decreasing the difficulties in taking aminosalicylates.