Background: One of the most commonly used patient reported outcome (PRO) measures in oncology is the European Organisation for Research and Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). In a recent publication by EORTC Quality of Life Group, global HRQoL (gHRQoL), a single higher order measurement model for QLQ-C30, was found to be robust and is recommended to supplement the traditional 15-outcome profile. Aim of this study is to evaluate longitudinal gHRQoL from diagnosis to year 5 after end of treatment (y5EOT ) in GHSG clinical trials for early-stage favorable (HD13), early-stage unfavorable (HD14) and advanced-stage (HD15) HL. Methods: 5,306 qualified patients of the HD13-HD15 trials (ISRCTN63474366, ISRCTN04761296, ISRCTN32443041) ≤60 years at study entry were eligible for evaluation; 4 ,110 provided HRQoL data. Patients were treated with different risk-adapted therapies . EORTC QLQ-C30 was used to evaluate gHRQoL from diagnosis to y5EOT with means and 95% confidence intervals. Treatment effects on gHRQoL in y2EOT and y5EOT were tested with multiple linear regression analyses adjusting for age, gender and baseline-gHRQoL. Results: Analysis showed significantly worse baseline-gHRQoL with higher stage (means [95%-CI]: HD13 80.6 [79.5-81.8], HD14 76.1 [75.2-77.0], HD15 71.0 [70.0-71.9]). During chemotherapy, gHRQoL worsened in all stages (means [95%-CI]: HD13 63.5 [62.2-64.8], HD14 62.8 [61.9-63.8], HD15 62.7 [61.9-63.6]), rapidly improving thereafter. Compared to baseline, gHRQoL in the early-stage group recovered and remained stable from y1EOT, whereas in higher stages it improved significantly above baseline value, also remaining stable during follow up (y5EOT means [95%-CI]: HD13 82.6 [80.8-84.4], HD14 83.9 [82.6]85.1, HD15 82.5 [81.4-83.7]) (Figure). Age- and gender-adjusted German reference values of gHRQoL (93.5-93.9 in HD13-HD15) were not reached at any time point. Comparison of standard vs. successful experimental treatments showed that treatment intensity had no significant influence on long-term gHRQoL. Age and baseline gHROoL were predictive of gHRQoL in y2EOT and y5EOT. Conclusion: Global HRQoL is largely impaired among HL patients. Despite significant baseline differences, gHRQoL after therapy seems independent of initial stage or treatment regimen and does not recover to normal values, warranting further investigation. QLQ C30 summary score seems like a promising tool for PRO evaluation, encouraging further testing.