PURPOSE: The purpose of this study was to estimate prevalence of fatigue, identify correlates of fatigue and evaluate the relationship between fatigue and health-related quality of life (HRQOL) in a large cohort of disease-free breast cancer survivors. METHODS: Participants are enrolled in the HEAL Study, a multi-center prospective study of women diagnosed with in-situ to Stage IIIA breast cancer. HEAL participants (n = 1183) completed a baseline and a 24-month follow-up interview. Women in this report (n = 800) also completed a quality of life questionnaire that included the Piper Fatigue Scale and the RAND SF-36 two to five years after diagnosis. Multivariate regression methods were used to identify significant factors associated with fatigue. SF-36 scores for fatigued survivors were compared to non-fatigued survivor scores and population norms. RESULTS: Forty-one percent of the breast cancer survivors were fatigued. Significant correlates of fatigue included pain, cognitive problems, physical inactivity, weight gain/personal appearance and antidepressant use. Fatigue was associated with poorer HRQOL, most notably in areas of role and social functioning. CONCLUSION: This study provides further support for the conclusion that a significant proportion of breast cancer survivors experience fatigue that compromises HRQOL two to five years post-diagnosis.