Ten male subjects affected by sickle cell anemia (SCA) were studied to evaluate the long-term effects of therapies on their fertility. Their ages ranged from 18 to 34 years (median: 32 years). Four subjects were treated by hydroxyurea (HU) and 6 by hematopoietic stem cell transplantation (HSCT). The median follow-up after HU initiation and HSCT was 10.5 years (range: 8-15 years) and 15.5 years (range: 8-21 years), respectively. Three of the 6 in the HSCT group and two of the 4 in the HU group were azoospermic. One HSCT subject had normal semen and hormone variables, showing that normal fertility can occasionally be expected after transplantation in SCA. The remaining 4 patients (2 HSCT and 2 HU) were oligozoospermic. With regard to HU, semen impairment appears to be related to the duration of treatment. To draw general conclusions, further research with a large number of patients treated since childhood with HU or HSCT is warranted.