Background: Hypothyroidism is a common condition of thyroid hormone deficiency. Patient's knowledge and awareness about diseases and its treatment is very important for good long-term outcomes. Aim: The study was aimed to evaluate the effect of an educational protocol on hypothyroidism patients' knowledge and practice. Research design: A quasi-experimental research design was utilized. Setting: The study was conducted in Outpatient clinics at Benha University Hospital and Educational Hospital affiliated to Ministry of Health Qalyubia Governmental, Egypt. Sample: A purposive sample composed of 60patients with hypothyroidism. Tools: Two tools were utilized to collect data: 1) A Structured assessment questionnaire which consisting of two parts: A) Patients' personal data and medical history. B) Patients' knowledge assessment. 2) Patients' Practice Assessment. Results: There was a marked improvement in patients' knowledge and practice regarding hypothyroidism with a highly statistically significant difference between pre and post implementing of an educational protocol. Conclusion: The educational protocol had been proved to be significantly effective in improvement of studied patients' knowledge and practice regarding hypothyroidism. Recommendations: Orientation programs on mass Medias for measuring thyroid function in all adults specially at age of 35 years and every 5 years, more frequent screening for high risk or symptomatic individuals. Further research is needed on a larger probability sample at different settings to generalize the results.