Hypothyroidism is a globally prevalent condition with a huge impact on health. It has been demonstrated that hypothyroidism is associated with negative health outcomes that have a significant impact on quality of life. The aim of this study is to assess the relative significance of various parts of quality of life satisfaction in adult patients with hypothyroidism. This study has never been done in Saudi Arabia. No previous research was conducted in our region to highlight the quality of life of these patients. From this, it is very important to acknowledge the impact of hypothyroidism on quality of life, to help improve their lives and reduce the burden of the disease. MethodThis is a case-control study conducted on patients with hypothyroidism presented to the family medicine clinic at King Abdulaziz University Hospital. The participants were divided into two groups: patients with primary hypothyroidism (cases) and euthyroid subjects of the same age without chronic illnesses (control group). We used the Short Form-12 questionnaire (SF-12) and a sociodemographic questionnaire as a tool to assess the quality of life. ResultsCompared to healthy euthyroid controls, patients with hypothyroidism had a significantly reduced quality of life regarding their physical (p<0.001) aspect, with mental health not being affected. Smoking, female gender, and BMI showed significant associations with their mental health status (p=0.021, p=0.001, and p=0.045) respectively. ConclusionsRegarding the results of the current study, there is a reduced level of physical health in patients with hypothyroidism than in healthy controls, which adversely affects their QoL. Smoking, gender, and BMI were associated with lower mental health among patients with hypothyroidism, which adversely affected their quality of life. Health practices should include assessment of the quality of life, monitoring by specialized physicians, and educational programs for these patients.