7518 Background: Cardiorespiratory fitness is a well-established independent predictor of all-cause mortality in a broad range of adult populations. The association between cardiorespiratory fitness and mortality has not been investigated among individuals diagnosed with cancer. We examined the association between cardiorespiratory fitness and all-cause mortality in 398 patients with non-small cell lung cancer (NSCLC). Methods: Using a prospective, observational design, patients with known or suspected NSCLC enrolled in CALGB 9238 were studied. Prior to pulmonary resection, all participants performed an incremental exercise test with expired gas analysis to assess cardiorespiratory fitness (i.e., peak oxygen consumption; VO2peak) and were observed for death or until June 2008. Cox proportional hazards models were used to estimate the risk of all-cause mortality according to cardiorespiratory fitness category defined by VO2peak (<0.96 / 0.96–1.29 / >1.29 L.min-1) with adjustment for age, gender, and performance status. Results: Of the 398 patients, 335 underwent surgical resection and 63 were deemed not eligible for resection. Median follow-up was 30.8 months, 294 deaths were reported during this period. For the entire sample, mortality rates declined across increasing VO2peak categories (adjusted Ptrend= 0.012). Compared with patients achieving a VO2peak <0.96 L.min-1, the adjusted hazard ratio (HR) for all-cause mortality was 0.64 (95% CI, 0.46 to 0.88) for a VO2peak of 0.96–1.29 L.min-1, and 0.56 (95% CI, 0.39 to 0.80) for a VO2peak of >1.29 L.min-1. The corresponding HRs for surgical patients were 0.65 (95% CI, 0.44 to 0.96) and 0.62 (95% CI, 0.42 to 0.90) relative to the lowest VO2peak category (ptrend=0.03), respectively. For non-surgical patients, the HRs were 0.74 (95% CI, 0.32 to 1.75) and 0.43 (95% CI, 0.18 to 1.00) relative to the lowest category (ptrend<0.04). Conclusions: Low VO2peak is associated with poorer survival among surgical candidates with NSCLC. Further work is required to investigate the prognostic value of objective measures of functional capacity in NSCLC and other cancer populations. No significant financial relationships to disclose.