Background: Quality of life deteriorates due to unhealthy behaviors. Unhealthy lifestyle practice is high in west Ethiopia; it leads to poor quality of life, however, no intervention is given. Objective: To evaluate the effect of a lifestyle education intervention on quality of life in healthy middle-aged urban residents. Methods: A quasi-experimental design was applied from 1st February to 30th July 2019 on 266 unscreened healthy adults aged 41-64 years. A faceto- face educational approach was reinforced on 133 intervention participants. The status of quality of life was measured at baseline and post of six-month intervention using EQ-5D tools. Statistical significance was described at p ≤ 0.05. Results: Intervention group showed significant improvement of health-related quality of life as compared to the control group in six-month lifestyle changes. In the intervention group, the prevalence of poor quality of life declined by 1.2% as compared to baseline. Likewise, physical activity level, diet diversity, and sleep pattern showed improvement due to lifestyle education intervention. Prevalence of poor quality of life scores significantly declined by 2.5% (p<0.001) among participants who had pain/discomfort in the intervention group. With sex-stratified, usual activity difficulty decreased the male’s quality of life by more than five times (OR: 5.44; 95% CI 1.28-23.04, p=0.022) as compared to females. Conclusion: Community-based lifestyle education targeted to middle-aged adulthood significantly improved health-related quality of life in western Ethiopia.