OBJECTIVES: The aim of this paper is to describe the relationship between smoking status, dietary habits, physical activity and alcohol intake, and mental and physical self-reported health in a general population. MEASURES: A large population-based study Inter99, Copenhagen, Denmark, 1999-2006. Self-reported health-related quality of life was measured by Short Form 12 (SF-12). Mental and physical health component scores were computed. RESULTS: At baseline, SF-12 was completed by 6305 (92.3%) participants in the intervention groups, and 3017 (72.4%) persons in the control group. In cross-sectional analyses, persons with an unhealthy lifestyle reported significantly worse physical and mental health than persons with a healthier lifestyle. In longitudinal data, using adjusted multivariate analyses (N=3,084), we found an association between increased physical activity at five-year follow-up and improvement in physical health ( odds ratio=2.30 (95% confidence interval=1.7-3.2)) in the high-intensity intervention group. Improvement in mental health was associated with a much healthier diet at 5-year follow-up than at baseline ( odds ratio=1.68 (95% confidence interval=1.1-2.5)). CONCLUSIONS: This study describes the negative relationship between unhealthy lifestyle and self-reported mental and physical health in a general population. Also, it shows the impact of improvements in lifestyle on self-reported health in a general population, which has not been investigated before.