['We sought to examine whether change in physical activity energy expenditure (PAEE) is associated with change in metabolic risk factors and whether this association is independent of change in fat mass and aerobic fitness.', 'In a population-based sample of 176 men and 217 women followed prospectively for 5.6 years, we measured PAEE by individually calibrated heart rate monitoring, aerobic fitness, total body fat (fat mass), and metabolic risk factors (blood pressure, fasting triglycerides, HDL cholesterol, insulin, and 2-h glucose) at baseline and follow-up.', 'A 100 J x kg fat-free mass (FFM)(-1) x min(-1) increase in PAEE from baseline to follow-up reduced triglycerides by 3.5% (95% CI 0.03-5.7) in men and 3.2% (0.02-5.4) in women, fasting insulin by 5.3% (1.0-7.5) in men and women, and 2-h glucose by 3.2% (0.3-5.3) in men and 3.1% (0.3-5.2) in women, after adjustment for sex, age, smoking status, aerobic fitness, baseline phenotype, and change in fat mass. In general, the magnitudes of association for change in fat mass with metabolic risk factors were two to three times stronger than for PAEE.'] Is increase in physical activity energy expenditure associated with reduced metabolic risk independent of change in fatness and fitness?