Background: More awareness regarding the postmenopausal syndrome (PMS) is needed for women to leading a quality life. Postmenopausal symptoms adversely affect the life expectancy and quality of life (QoL) of women. The aim of this study was to determine the knowledge and awareness regarding the postmenopausal syndrome among women above 30 years in Quetta, Pakistan. This study was to assess the amount of knowledge women have about postmenopause, its causes, symptoms, diagnosis, treatment, and complications. Materials and methods: A cross-sectional, interview-based survey was conducted from January to September 2016. An estimated 447 women (aged above 30 years) were selected. Their knowledge about the postmenopausal syndrome was assessed by a structured questionnaire. A convenient sampling technique was used to collect data. Results: A total of 550 questionnaires were distributed, of which 447 were returned (response rate: 81%). The mean age of the respondents was 38.06 ± 6.194 years. The mean of the total knowledge score was 12.77 ± 3.910. Totally, 53.0% had adequate knowledge regarding the postmenopausal syndrome and 47.0% had a poor knowledge regarding the postmenopausal syndrome. A total of 73.5% of the respondents were aware of the age of menopause. Majority of the respondents know the causes of the postmenopausal syndrome. An estimated 45.3% knew that it can be diagnosed by a blood test. A total of 43.8% did not know about the hormone replacement therapy used for the treatment of the postmenopausal syndrome. Conclusion: The purpose of this study was to assess the knowledge among Quetta women regarding the postmenopausal syndrome, its causes, symptoms, diagnosis, treatment, and complications. This study found that the knowledge among women regarding the postmenopausal syndrome is important for improving their QoL and for managing the symptoms of the postmenopausal syndrome. The study participants showed an adequate level of knowledge about the postmenopausal syndrome; however, there were areas of knowledge that need improvement by health education. Healthcare professionals should give all the necessary information to women about the postmenopausal syndrome. The ratio of poor knowledge can be improved by raising the awareness and increasing the education level of women.