Objective The present work aimed at determining the prevalence of menopausal symptoms and factors associated with the Quality of life among postmenopausal women. Materials and methods This cross-sectional work was carried out on 270 postmenopausal females referring to health centers of Hamadan city chosen by stratified random sampling. A questionnaire of the Menopausal Quality of Life Questionnaire (MENQOL) was used as the data collection method. Although, the Mann–Whitney test and the Kruskal–Wallis tests were used to compare MENQOL item scores. The significance level of statistical tests was regarded as less than 0.05. Results The mean MENQOL Score in menopausal was 2.45 ± 1.04. Also, vasomotor symptoms had the highest score, and sexual symptoms had the lowest score rather than other dimensions. There was a significant association between the total menopausal quality of life score and job, economy status, smoking, exercise, supplemental Omega-3 s intake, and Postmenopausal stage (p < 0.01). As smokers, women had increasing levels of bother experienced from the MENQOL symptom than non-smokers (mean = 3.67 ± 0.85 vs. 2.36 ± 0.99; p < 0.001). While the MENQOL scores for menopausal females who exercised more often (mean = 1.56 ± 0.7) had lower than those who exercised less than 3 times per week (mean = 3.27 ± 0.9; p < 0.001). However the lowest score was menopausal females who had taking supplemental Omega-3 s than those who hadn't taken it (mean = 2.15 ± 1.06 vs. 2.65 ± 0.97; p < 0.001). Though women who had postmenopausal stage less than 5 years stage (mean = 2.28 ± 0.87) had significantly lower MENQOL scores from those who had postmenopausal stage 5 or more years (mean = 2.63 ± 1.16; p < 0.001). Conclusion Based on the results, vasomotor symptoms were the most dominant symptom. Therefore, it is necessary to improve physical activity levels, focusing on job status, recommend taking an omega 3 s supplement, and planning education and promotion intervention for cessation or prevention of smoking among postmenopausal women to increase the MENQOL is essential.