BACKGROUND: The aims of this study were to externally validate an established association between baseline health-related quality of life (HRQOL) scores and survival and to assess the added prognostic value of HRQOL with respect to demographic and clinical indicators. METHODS: Pooled data were analyzed from 17 randomized controlled trials opened by the Canadian Cancer Trials Group between 1991 and 2004; they included survival and baseline HRQOL data from 3606 patients with 8 different cancer sites. The models included sex, age (≤60 vs >60 years), World Health Organization performance status (0 or 1 vs 2-4), distant metastases (no vs yes), and 15 European Organization for Research and Treatment of Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQ-C30) scales. Analyses were conducted with multivariate Cox proportional hazards models and were stratified by cancer site. Harrell's discrimination C-index was used to calculate the predictive accuracy of the model when HRQOL parameters were added to clinical and demographic variables. The added value of adding HRQOL scales to clinical and demographic variables was illustrated with Kaplan-Meier curves. RESULTS: In the stratified, multivariate model, HRQOL parameters—global health status (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.95-1.00; P <. 0001), dyspnea (HR, 1.04; 95% CI, 1.02-1.06; P <. 0002), and appetite loss (HR, 1.06; 95% CI, 1.04-1.08; P <. 0001)—were independent prognostic factors in addition to the demographic and clinical variables (all P values <.05). Adding these HRQOL variables to the clinical variables resulted in an added relative prognostic value for survival of 5%. CONCLUSIONS: These results confirm previous findings showing that baseline HRQOL scores on the EORTC QLQ-C30 provide prognostic information in addition to information from clinical measures. However, the impact of specific domains may differ across studies. Cancer 2018. © 2018 American Cancer Society.