Transfusion-dependent thalassemia (TDT) is a group of thalassemia syndromes that require regular blood transfusions for survival. It is unknown whether the sense of smell of patients with TDT is affected, and if so, whether smell loss has an adverse effect on quality of life (QOL). Olfactory thresholds were measured using Snap & Sniff(A (R)) wands. QOL was assessed via the Short Form-36 (SF-36) questionnaire. Forty-two TDT patients from the Thalassemia Center in Istanbul Medical Faculty were tested (mean age 26.6 years), along with 42 healthy controls (mean age 28.0 years). Mean olfactory sensitivity was lower in the TDT patients than the controls (p < 0.0001). TDT was associated with lower mean QOL scores on the domains of physical function (p < 0.0001), physical role limitation (p = 0.011), and general health (p < 0.0001). Within the TDT group, significant correlations were present between the threshold scores and physical function, physical role limitation, emotional role limitation, and general health. Patients with TDT are less sensitive to odors than healthy controls and the lower olfactory test scores are related to lower quality of life, suggesting that decreased smell function is an additional complication of this disease.