Background Data on the prevalence and type of endocrine disorders in beta-thalassemia intermedia (beta-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of beta-TI patients. Methods In this cross-sectional multicenter study, 726 beta-TI patients, aged 2.5-80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 +/- 12.1; range: 2.5-80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. Results Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729-13.099,P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944-13.521,P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217-140.968,P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012-2.977,P = 0.045). Hydroxyurea was identified as a "protective factor" for NIDDM (Odds ratio: 0.259, 95% CI: 0.074-0.902,P = 0.034). Conclusions To the best of our knowledge, this is the largest cohort of beta-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with beta-TI compared with beta-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in beta-TI patients.