Factors associated with spermatogenesis after allogeneic hematopoietic stem cell transplantation (HSCT) were assessed in this prospective, single-center, cross-sectional study. All consecutive men aged 18 years or older and in complete remission 2 years or longer after HSCT were invited to participate. Seminal fluid analysis was performed on freshly collected samples according to World Health Organization guidelines. Between April 2003 and June 2004, 39 patients were included. The median age at semen analysis was 34 years (range, 20-59 years), and the median time interval between HSCT and sperm analysis 9 years (range, 2-20 years). Thirty-two patients (82%) underwent total body irradiation (TBI; >or= 10 Gy) as part of their conditioning regimen. Eleven of 39 (28%) patients showed some spermatogenesis. Patients with detectable spermatozoa in the ejaculate were younger at HSCT (median age, 19 versus 28 years; P = .004), had a longer interval since HSCT (median time, 12 versus 7 years; P = .01), and were more often without chronic graft-versus-host disease (GvHD; 2 of 11 patients versus 16 of 28; P = .03). Nine of 16 patients (56%) undergoing transplantation when younger than age 25 years showed some degree of spermatogenesis. In conclusion, men who are long-term survivors, who were younger than 25 years at HSCT, and who apparently do not have chronic GvHD have a reasonable likelihood of spermatogenesis even when conditioned with standard-dose TBI.