The occurrence of collagenous colitis (CC) in patients with pre-existing inflammatory bowel diseases (IBD) is rare, with only seven cases reported in the past. Herein, we report two IBD cases who developed CC after successful treatment of their IBD with two different tumor necrosis factor (TNF)-α inhibitors, which have been previously reported to successfully treat refractory CC. This report highlights the need to do random biopsies of the colon for CC diagnosis in IBD patients with symptoms of diarrhea after complete mucosal healing. The report also reviews plausible mechanisms as to how CC may develop, including the role of multiple medications.