Purpose: This study was conducted to examine the effects of uncertainty, social support, and sick role behavior on health-related quality of life in patients with peripheral arterial disease. Methods: This study is a descriptive research using self-reporting questionnaire. Data were collected from 167 patients with peripheral arterial disease. Measurement tools were Multidimensional Scale of Perceived Social Support(MSPSS), Mishel's Uncertainty in Illness Scale (MUIS), Sick role behavior measurement tools and SF-36 Version I. The data were analyzed using descriptive statistics, correlation, and regression analysis by using SPSS/WIN 24.0. Results: Factors that significantly influenced physical health-related quality of life were age (β=-.19, p=.010), monthly income (β=.17, p=.027), uncertainty (β=-.29, p<.001), and exercise and rest (β=.28, p<.001) that all together accounted for 32.6% of the variance. Factors that significantly influenced mental health-related quality of life were monthly income (β=.20, p=.015), drinking (β=.17, p=.040), uncertainty (β=-.24, p=.001), and exercise and rest in sick role behavior (β=.26, p=.003) that all together accounted for 18.2% of the variance. Social support was an insignificant factor on physical and mental health-related quality of life. Conclusion: To improve the health-related quality of life of people with peripheral arterial disease, it is necessary to develop a systematic nursing intervention program including a strong support system, education, strategies for alcohol abstinence, and exercise and rest therapy.