Background: The clinical determinants of six-minute walk test (6-MWT) performance in patients with left ventricular systolic dysfunction (LVSD) have rarely been investigated, and it is not clear whether they differ from patients referred for the assessment of symptoms of heart failure who do not have major structural heart disease (MSHD). Methods and Results: 571 patients with LVSD enrolled in a chronic disease management programme (79% male; mean age 71 10 years; BMI 28 +/- 5) completed a 6-MWT with a mean distance 337 103 m. 688 patients referred with suspected heart failure but in whom MSHD was excluded (49% male; mean age 70 11 years; BMI 28 6) had a mean 6-MWT distance of 391 106 in (P < 0.001 compared to patients with LVSD). Relationships with walking distance were determined by calculating odds ratios (ORs) with 95% confidence intervals (CIs) for walking <= 300 versus >= 300 m. In patients with LVSD, predictors of poor walking distance (:5300 in) included age >= 75 years (OR=4.0, 95% CI=2.4-6.4); low BMI (< 20) (OR=3.4, 95% 0=1.6-7.3); anaemia (OR=2.8, 95% CI=1.8-4.2); resting heart rate > 80 beats-min(-1) (OR=2.2, 95% CI=1.3-3.5); and being female (OR=2.0, 95% CI=1.3-3.0). Serum creatinine and NT-proBNP showed dose-response effects, as did self-perceived feelings of depression and anxiety. Determinants of 6-MWT in patients without MSHD were similar including age > 75 years (OR=6.0,95% CI=3.4-10.4), anaemia (OR=2.8, 95% CI=1.6-4.9), resting HR > 80 beats-min-1 (OR=2.5, 95% CI=1.4-4.4) and being female (OR=1.6, 95% CI=1.9-2.4). NT-proBNP and self-perceived feelings of depression and anxiety also showed dose-response effects. Conclusion: The determinants of poor 6-MWT performance depend on physical-cardiovascular and non-cardiovascular, and psychological factors. Clinical predictors for poor walking performance are similar for patients with LVSD and without MSHD. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.