Hypothyroidism is the second most important endocrine disorders, and its prevalence reaches 7% worldwide. There are many etiologies of hypothyroidism, and where a low knowledge coupled with inadequate health literacy may lead to poor disease control, prevention and adherence. This study aimed to explore the main etiology of hypothyroidism at Petra region, and measure patients' knowledge, awareness and practice (KAP) according to the hypothyroidism and adherence to treatment. A cross-sectional study was conducted at Queen Rania Hopital. Hypothyroidism participants (n=150), aged ?18 years, from Petra, responded to the validated questionnaires. Blood samples were collected to measure antithyroid antibodies. A total of 150 participants completed the questionnaire. The median age of the participants was 41.5 ± 13.5 years; with the majority being females (92.7%). Blood analysis showed that 62.7% of the sample had positive antithyroid antibodies which are the highest prevalent risk factor in the region, the life style and iodine intake as second risk factors, 62% of patients had a family history and 20.1% of females diagnosed during pregnancy or postpartum. Also, other diseases showed high risk such as diabetes (22.7%) and vitamin D3 deficiency (36%). According to the total score of KAP majority of the sample had poor and low level of knowledge and awareness regarding hypothyroidism. In addition to, 82% of participants were adherent to thyroxine, and the proportion of patients whose thyroid hormonal level was controlled was 56.7%. This study concluded that a large number of patients were lacking basic knowledge about hypothyroidism and they had dietary and treatment-related misconceptions, which may affect disease controlling and adherence to treatment. Thus, health care providers should educate and counsel patients in order to improve their knowledge regarding disease and adherence. The most prevalent etiologies of hypothyroidism are female gender, autoimmunity (Hashimoto's), family history, the geographical region of Petra, life style and poor iodine intake.