Background Endocrinopathies and metabolic complications are common in beta thalassemia major patients receiving blood transfusions. Chelation therapy has a role in preventing or delaying such complications. However, patients may face difficulties adhering to chelation therapy for several reasons. Aim To evaluate endocrine complications in beta thalassemia major patients (2–30 years) in the Eastern Province of Saudi Arabia and compare the onset of endocrine complications among compliant and noncompliant patients. Moreover, we assessed the barriers that hinder compliance with chelating therapy. Methods A cross-sectional study was conducted on 89 patients (43 males and 46 females) aged 2 to 30 years attending different hospitals in the Eastern Province of Saudi Arabia. A semi-structured questionnaire was used to collect demographic data and medical histories. The questionnaires were completed by face-to-face interviews with the patients or their caregivers, and the required laboratory data were retrieved from the medical records of patients. Results The most prevalent abnormality was underweight detected in (40.9%) of patients, followed by subclinical hypothyroidism (37.7%), short stature (35.2%), hypothyroidism in (17.0%) and diabetes mellitus in (13.6%). A significant difference between those who were compliant with iron chelation therapy and those who were not in terms of the prevalence of short stature ( P value= 0.05 ) and hypothyroidism ( P value= 0.05 ). The percentage of patients who were not compliant with chelation therapy was 21.6% and 9.1% of patients were not taking them at all. Conclusion Despite the role of chelation therapy in the management of iron overload, the risk of secondary endocrine and metabolic complications remained considerable. Subclinical hypothyroidism and short stature were the most frequent endocrine complications encountered in this study.