Ulcerative Colitis (UC) tends toward a chronic relapsing pattern in most patients. Predicting severity of disease course in Ulcerative Colitis is important to achieve optimal relapse prevention, limit hospitalizations, and prevent surgery. The aim of the current study was to examine which factors might be associated with a disease relapse in a high risk group of patients with inactive UC. 49 patients with inactive UC were recruited into the study. UC subjects had a documented moderate to severe flare in the last 6 months (Mayo Score >6), but were inactive at the time of enrollment (Mayo Score <2). All subjects were on a stable course of medications (5ASA, immunomodulators, biologics, and off prednisone) for at least 3 months before enrollment. All subjects underwent a gastroenterologist visit with a clinical assessment, blood draw, stool collection, an unprepped flexible sigmoidoscopy with biopsies at the time of enrollment. In addition all subjects completed a series of validated psychosocial questionnaires including: IBD Quality of Life Questionnaire (IBDQ), Perceived Health Competence Scale (PHCS), Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Questionnaire (PSQ), and Mindful Attention Awareness Scale (MAAS). Patients were then followed up in the study at 8 weeks, 6 months, and 12 months with all the same measures at enrollment. If patients developed symptoms of a flare during the trial they were seen by the study gastroenterologist. Of the subjects that flared, those that flared in the first 90 days were defined as “early flare.” The remainder of patients who flared were then defined as “late flare.” Baseline factors were then examined to determine which were associated with a disease flare. Statistical calculations were performed by Cox proportional model analysis. Over the course of the 12 month study 28/49 subjects had a disease relapse (57%). 11 patients had an early flare, and 17 had a late flare. In our study baseline factors that were associated with an early flare included elevated IL-6, Mayo Score, and lack of normal vascularity or mild granularity on first endoscopy (P < 0.05). Baseline factors not significantly associated with an early disease flare included pathology, cytokines (TNF, IL-8, and IL-10), stool calprotectin, urinary cortisol, validated psychological questionnaires, or quality of life. Patients with UC are at significant risk of disease relapse. Factors such as a mild increase in clinical disease activity (Mayo Score 1 or 2), elevated IL-6, or loss of normal vascular pattern or mild granularity on endoscopy were associated with a relapse of disease. Findings on pathology, stool calprotectin, and symptoms of stress, depression, or decreased quality of life were not able to accurately predict a disease flare. Further studies are needed to confirm these findings, but adding IL-6, a noninvasive marker of disease activity, or noting subtle changes in endoscopic findings may be important in clinical decision making to limit disease relapse.