Background: The extent to which uncomplicated obesity among an otherwise healthy middle-aged population is associated with higher longitudinal health-care expenditures remains unclear., Methods: To examine the incremental long-term health service expenditures and outcomes associated with uncomplicated obesity, 9398 participants of the 1994-1996 National Population Health Survey were linked to administrative data and followed longitudinally forward for 11.5 years to track health service utilization costs and death. Patients with pre-existing heart disease, those who were 65 years of age and older, and those with self-reported body mass indexes of <18.5 kg/m² at inception were excluded. Propensity-matching was used to compare obesity (+/- other baseline risk-factors and lifestyle behaviours) with normal-weight healthy controls. Cost-analyses were conducted from the perspective of Ontario's publicly-funded health care system., Results: Obesity as an isolated risk-factor was not associated with significantly higher health-care costs as compared with normal weight matched controls (Canadian $8,294.67 vs. Canadian $7,323.59, P = 0.27). However, obesity in combination with other lifestyle factors was associated with significantly higher cumulative expenditures as compared with normal-weight healthy matched controls (CAD$14,186.81 for those with obesity + 3 additional risk-factors vs. CAD$7,029.87 for those with normal BMI and no other risk-factors, P < 0.001). The likelihood that obese individuals developed future diabetes and hypertension also rose markedly when other lifestyle factors, such as smoking, physical inactivity and/or psychosocial distress were present at baseline., Conclusions: The incremental health-care costs associated with obesity was modest in isolation, but increased significantly when combined with other lifestyle risk-factors. Such findings have relevance to the selection, prioritization, and cost-effective targeting of therapeutic lifestyle interventions.