Background: Cancer-related fatigue (CRF) is the most prevalent and distressing cancer-related symptom and has a greater negative impact on patients' daily activities and quality of life than other cancer-related symptoms, including pain and depression. However, the prevalence and severity of persistent CRF and related disability in the post-treatment survivorship period has seldom been examined in populations other than breast cancer. The primary objective of the study was to describe the prevalence of significant CRF and associated levels of disability in a mixed cancer population sample at 3 time points in the post-treatment survivorship trajectory. Methods: Based on cancer registry data, a self-administered mail based questionnaire using Dillman's Tailored Design Method was sent to 3 cohorts of disease-free cancer survivors (6-18 months; 2-3 years; and 5-6 years post-treatment) previously treated for non-metastatic breast, prostate or colorectal cancer. Fatigue was measured using the FACT-F and disability was measured with the WHO-Disability Assessment Schedule. Clinical information was extracted from chart review. Frequencies of significant fatigue by disease sites and time points were studied and compared using chi-square test. Disability between those with and without CRF was also compared using Cochran-Armitage trend test. Results: 1294 questionnaire packages were completed (63% response rate). The FACT-F score was 39.1+10.9; 29% (95% CI: [27%, 32%]) of the sample reported significant fatigue (FACT-F≤34) and this was associated with much higher levels of disability (p<0.0001). Breast (40% [35%, 44%]) and colorectal (33% [27%, 38%]) survivors had significantly higher rates of fatigue (≤34) compared to the prostate group (17% [14%, 21%]) (p<0.0001). Fatigue levels remained relatively stable across the 3 time points. Conclusions: CRF was a significant and debilitating symptom for a substantial minority of the respondents across all 3 time points. Effective CRF management strategies are needed and have the potential to significantly reduce morbidity associated with cancer and its treatments and to improve quality of life for the growing population of cancer survivors.