Background: Given the high prevalence of depression in the elderly, as well as the importance of health-related lifestyle in the prevention of aging, this study was designed to compare the health-promoting lifestyle in elderly with depression and healthy elderly. Methods: This was a cross-sectional study on 200 elderly over 60 years of age referred to health care centers in Isfahan City, Iran, during the year 2018. Demographic information, health-promoting lifestyle (Walker and Hill-Polerecky questionnaire), and depression [Geriatric Depression Scale (GDS) short form] were recorded and analyzed. Findings: The prevalence of depression among 200 elderly was 59. 1%, and the initial analysis showed a significant relationship between marital status, education, and all aspects of health-promotion lifestyle (nutrition, exercise, responsibility for health, stress management, interpersonal support, and self-healing) and depression. However, after adjusting for all factors in multivariate regression analysis, there was significant independent and inverse relationship between the dimensions of stress management [odds ratio (OR) = 0. 76; confidence interval (CI): 0. 99-0. 58) and responsibility (OR = 0. 75; CI: 0. 90-0. 62) and depression in the elderly. Conclusion: Onwards of health-promoting lifestyle, stress management, and health responsibility in elderly with depression is poorer than healthy ones.