Metabolic syndrome confers an increased risk of cardiovascular disease (CVD) in the general population. The relationship between adiponectins, and clinical outcomes in patients undergoing hemodialysis remains controversial. We investigated whether adiponectins, biomarkers of inflammation, nutrition status and clinical features predict the mortality of patients undergoing hemodialysis for 6 years. We measured baseline plasma total and high-molecular-weight (HMW) adiponectins, tumor necrosis factor (TNF)-α, serum high sensitivity C-reactive protein (hsCRP), and clinical characteristics including visceral fat area (VFA) and the Geriatric Nutritional Risk Index (GNRI) in 133 patients undergoing chronic hemodialysis. Forty-one of the 133 patients died during follow-up. The deceased patients were significantly older, had more prior CVD and diabetes, higher TNF-α and hsCRP levels but lower GNRI. VFA, and total and HMW adiponectin did not significantly differ between the two groups. TNF-α and hsCRP levels and GNRI score were significant for predicting all-cause and cardiovascular mortality in receiver operating curve analyses. When stratified by a GNRI score of 96, Cox proportional hazards analyses identified TNF-α as a significant predictor of all-cause mortality (hazard ratio [HR] 1.23; P = 0.038) and hsCRP as a significant predictor of all-cause and cardiovascular mortality (HR, 2.32, P = 0.003; HR 2.30, P = 0.012, respectively) after adjusting for age, sex, diabetes mellitus, and prior CVD, only in malnourished patients. These results demonstrate that malnutrition and the inflammatory markers TNF-α and hsCRP, but not metabolic markers, including VFA and adiponectins have a significant impact on 6-year all-cause and cardiovascular mortality in Japanese patients undergoing hemodialysis.