9599 Background: We have previously identified overall a single-item measure for baseline quality of life (QOL) as a strong prognostic factor for survival (Tan, ASCO 2008), and that fatigue was an important component of patient QOL (Sloan, 2007). To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 NCCTG and MCCC oncology clinical trials of the effect of baseline fatigue on OS. Methods: 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0–100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0–50, n=1,497) vs not clinically deficient fatigue (nCDF, score 51–100, n=2,418). Cox proportional hazards models adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Results: Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 mos vs >83.9 mos, p<0.0001). The effect sizes were consistent across different disease sites (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR=1.23, p=0.02). Conclusions: Fatigue is a strong prognostic factor for OS independent of overall QOL and PS in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. No significant financial relationships to disclose.