While β-thalassemia major (β-TM)–related physiological complications have been well established, less is known about implications for neuropsychological and cognitive function. The few existing studies have focused almost exclusively on children. We evaluated cognitive function in adult β-TM patients compared to healthy controls (study 1) and in β-TM patients before and after blood transfusion (study 2). Performance intelligence quotient (IQ) was evaluated with four subtests from the Wechsler Adult Intelligence Scale (WAIS-III). Attention functions were evaluated using the online continuous performance test (OCPT). The results of study 1 revealed poorer performance of β-TM patients on three of the four intelligence subtests, with significantly lower total performance IQ scores compared with controls. The percentage of participants with abnormal performance IQ (<85) was almost five times higher in the β-TM group (58%) than in the control group (12%). In study 2, significant differences were found in OCPT performance as a function of blood transfusion. Before transfusion, patients had higher rates of omission and commission errors, slower response times (RTs), and lower RT consistency than after transfusion. As β-TM patients' life expectancy is increasing, assessment and treatment of neurocognitive functions should become an integral part of appropriate follow-up to improve patients' quality of life.