Fatigue is the most common and distressing symptom reported by patients undergoing radiation therapy (RT). However, limited information is available on the trajectories of fatigue, as well as on the predictors of interindividual variability in fatigue. This study evaluated a sample of patients who underwent RT for prostate cancer to examine how ratings of evening and morning fatigue changed from the time of simulation to four months after the completion of RT and to investigate whether specific patient, disease, and symptom characteristics predicted the initial levels of fatigue and/or characteristics of the trajectories of evening and morning fatigue. Using hierarchical linear modeling, a large amount of interindividual variability was demonstrated in the trajectories of evening and morning fatigue. Findings from this study suggest that younger men with a higher level of fatigue at the time of the simulation visit were at increased risk for higher levels of evening and morning fatigue over the course of RT. In addition, the level of morning fatigue over the course of RT appears to depend on the patient's level of depression at the time of the simulation visit. In future studies, the use of hierarchical linear modeling as an analytic tool will assist in the identification of patients who are most at risk for prolonged fatigue trajectories. This type of analysis may lead to the identification of subgroups of patients who are at higher risk for negative outcomes and who require different types of interventions for the fatigue associated with RT.