Purpose: We describe the short and intermediate-term quality-of-life (QOL) outcomes in patients treated on a randomized clinical trial in early-stage Hodgkin's disease (Southwest Oncology Group [SWOG] 9133) comparing subtotal lymphoid irradiation (STLI) with combined-modality treatment (CMT). Patients and Methods: Two hundred forty-seven patients participated in the QOL study (SWOG 9208), completing several standardized instruments (Symptom Distress Scale; Cancer Rehabilitation Evaluation System - Short Form; Medical Outcomes Study 36-Item Short-Form Health Survey Vitality Scale; and a health perception item), as well as questions about work, marital status, and concerns about having children. This article reports on results from baseline before random assignment, at 6 months, and at 1 and 2 years after random assignment. Results: Patients receiving CMT experienced significantly greater symptom distress (P < .0001), fatigue (P = .001), and poorer QOL (P = .015) at 6 months than the STLI patients, reflecting a shorter time since completion of therapy in the CMT arm. Importantly, patients in the two groups did not differ on any outcomes at the 1 -and 2-year assessments. Both patient groups reported significantly more fatigue before treatment than healthy reference populations, and fatigue did not improve in either group after treatment. Conclusion: This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term decrease in QOL and an increase in symptoms and fatigue with treatment, which is more severe with CMT; by 1 year, however, CMT and STLI patients report similar outcomes. Fatigue scores for both arms were lower at baseline than scores for the general population and did not return to normal levels 2 years after random assignment. The mechanisms responsible for this lingering problem warrant further investigation. © 2003 by American Society of Clinical Oncology.