Purpose Long-term (C5 years) quality of life after colorectal cancer is not well described. The present study assessed quality of life (QOL) and psychological distress in colorectal cancer survivors more than 5 years to describe changes over time and antecedents of long-term outcomes. Method A prospective survey of a population-based sample of 763 colorectal cancer patients assessed sociodemographic variables, health behaviors, optimism, threat appraisal, and perceived social support at 5 months postdiagnosis as predictors of QOL and psychological distress 5 years post-diagnosis. Results QOL improved over time (P/0.01 for each measure); however, measures of psychological distress remained stable (P[0.07 for each measure). Risk factors for poorer QOL and/or greater psychological distress included: later stage disease, having a permanent stoma, rectal cancer, fatigue, smoking, being single, low social support, low optimism, and a more negative cancer threat appraisal. Being women, having a pet, having a private health insurance, and receiving both surgery and adjuvant treatment were protective. Conclusion Consistent with response shift theory, the antecedents of QOL after colorectal cancer are multifactorial and include predisposing socio-demographic, medical, and psychological variables. Psychosocial interventions that target both social support and threat appraisal may be effective for this patient group. Additional stepped-up support may be needed for people from a poorer social environment who have multiple risk factors for poorer adjustment. Health system effects require further investigation.