AIDS affects physical, mental, social, and psychological health status. One of the goals of Health for All in the 21st century is to improve the quality of life. This study is a randomized clinical trial conducted on 120 HIV-positive women. Women were administered assessment questionnaires to be completed during the structured interview. After sample collection, participants were divided randomly into 3 groups by using the table of random numbers, then, respectively, received educational intervention, empowerment program, and routine procedures offered by the center and were followed by refilling the questionnaires 12 weeks after intervention. Depending on the type of data, chi-square, analysis of variance, and paired t test were used, and SPSS version 16 was used for data analysis. The finding showed that knowledge increased after intervention in educational ( P = .02) and empowerment groups ( P = .006); also empowerment group indicated significant difference in psychological ( P = .006) and spiritual ( P = .001) domains and their total quality of life ( P = .004). According to this study, exposing HIV-positive women to empowerment education is effective in improving their quality of life.