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CONTEXT Patients with gastrointestinal cancers are at high risk for functional problems that are generally accompanied by a decline in their overall status and intense psychological distress. OBJECTIVES This study compares the level of functioning in individuals with gastric cancer (GC) and colorectal cancer (CRC) and analyzes whether improved functioning can be explained by patients' psychological status and coping strategies. METHODS This is a prospective, transversal, multicenter study in patients with nonmetastatic GC and CRC before initiating adjuvant chemotherapy. Participants answered questionnaires evaluating quality of life, including functioning (European Organization for Research and Treatment of Cancer Quality of Life questionnaire), coping strategies (Mini-Mental Adjustment to Cancer), and psychological distress (Brief Symptom Inventory-18). RESULTS Between December 2015 and July 2017, 266 patients with CRC and 69 patients with GC were consecutively recruited. A pathological level of functioning was more prevalent in people with GC than in those with CRC (20% vs. 5%). Individuals with GC presented worse functioning and more psychological distress and displayed more hopelessness, anxious preoccupation, and cognitive avoidance as coping strategies than those with CRC. Psychological distress and fighting spirit accounted for 40% of the functional status in GC patients, whereas psychological distress and hopelessness represented 58% of CRC patients' functional status. CONCLUSION Our findings suggest that level of functioning affects many subjects with GC and reveals the importance of developing interventions targeted at enhancing adaptive coping strategies before initiating adjuvant cancer treatment.