ABSTRACT: BACKGROUND:The aims of this study were to prospectively assess symptoms of anxiety and depression among survivors of colorectal cancer (CRC), to compare these survivors with a normative population, and to identify subgroups at risk for experiencing symptoms of anxiety and/or depression across a 4-year time period. Also, the impact on health-related quality of life (HRQOL) was studied. METHODS:The population-based Eindhoven Cancer Registry was used to select patients diagnosed with CRC between 2000 and 2009. The Hospital Anxiety and Depression Scale and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (HRQOL) were completed by patients in 2010 (n?=?2625 [73% response rate]), 2011, 2012, and 2013 and by an age- and sex-matched normative sample (n?=?315) in 2011. RESULTS:Patients reported a significantly higher prevalence of depression (19.0% vs 12.8%) and anxiety (20.9% vs 11.8%) in comparison with the norm. Anxiety was stable, whereas depression scores changed over time, although this was not clinically relevant. A longer time since diagnosis was associated with fewer depressive symptoms over time, whereas older age and being male were associated with less anxiety and more depression. Being married was associated with less anxiety and depression, and a low education level and comorbid conditions were associated with more anxiety and depression. Higher levels of symptoms of depression and anxiety were associated with a lower global quality of life and lower physical, role, cognitive, emotional, and social functioning over time. CONCLUSIONS:Because of the increased prevalence of depression and anxiety among patients with CRC and their negative effect on HRQOL, screening and referral are of the utmost importance, especially among those who are single, have a low educational level, and have comorbid conditions, even years after diagnosis and treatment. Cancer 2018;124:2621-8. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.