Background: Uterine leiomyomas are considered as a major source of complications and the most common cause of hysterectomy. Objectives: The aim of this study was to compare the quality of life in women with and without uterine leiomyoma referred to gynecology clinics of Shiraz University of Medical Sciences in 2018. Methods: In this cross-sectional study, a total of 126 patients who referred to the clinics of Shiraz University of Medical Sciences were selected and divided into equal groups according to uterine leiomyoma, 1 - 7 cm uterine leiomyoma group and non-uterine leiomyoma group by convenience sampling. The World Health Organization Quality of Life and Healthy Lifestyle questionnaires were used for data collection. Independent t-test was used to analyze the data. Results: The mean quality of life of women with uterine leiomyoma was 47.20 ± 12.41 and women without uterine leiomyoma had a significant difference (51.11 ± 11.23, t = 3.93, P = 0.041). The mean lifestyle of women with uterine leiomyoma was 114.18 ± 25.48 and women without uterine leiomyoma had 149.11 ± 23.81 (t = 4.01, P = 0.029). Conclusions: The mean score of quality of life and lifestyle were significantly different in women with and without uterine leiomyoma. Therefore, it is necessary to improve the quality of life of women by improving their lifestyle and providing psychological counseling.