Previous heart failure (HF) risk models have included clinical and noninvasive variables and have been derived largely from clinical trial databases or decompensated HF registries. The importance of hemodynamic assessment is less established, particularly in ambulatory patients with advanced HF. In this study, 513 consecutive ambulatory patients (mean age 54 ± 11 years, mean left ventricular ejection fraction 20 ± 9%) with symptomatic HF who underwent diagnostic right-sided cardiac catheterization as part of outpatient assessment from 2000 to 2005 were reviewed. After a total of 1,696 patient-years of follow-up, 139 (27%) patients had died and 116 (23%) had undergone cardiac transplantation. The 1- and 2-year overall survival rates (defined as freedom from death or cardiac transplantation) were 77% and 67%, respectively. Overall, 65% of patients had elevated intracardiac filling pressures, and 40% had cardiac indexes <2.2 L/min/m2. In multivariate analysis, mean pulmonary arterial pressure, cardiac index, and the severity of mitral regurgitation were the 3 strongest predictors of all-cause mortality and cardiac transplantation. Renal dysfunction was also an independent predictor of all-cause mortality. When a clinical model for Cox multivariate analysis of all-cause mortality was compared with a model that also included cardiac index and mean pulmonary arterial pressure, the chi-square score increased from 45 to 69 (p <0.0001). In conclusion, in ambulatory patients with advanced HF, hemodynamic and renal function assessments remain strong independent predictors of all-cause mortality.