Using the NAPRTCS database from January 1987 to January 2001, we examined 2687 adolescent (age 13-17 yr) index renal transplants to analyze differences in demographic treatment, and outcomes in adolescents with FSGS compared to other renal disease. 338 (12.6%) of adolescents had a primary diagnosis of FSGS. Adolescents with FSGS were more likely to be black and less likely to receive pre-emptive transplants (p < 0.001). No differences existed in HLA matching or immunosuppression regimens. Acute tubular necrosis occurred in more FSGS adolescents compared to non-FSGS adolescents following LD (11% vs. 4.7%) or CD (25.1% vs. 17.8%) transplants (p < 0.001). There were no significant differences in acute rejection rates between adolescents with FSGS and other adolescents. Graft survival was worse for LD FSGS adolescents (6 yr, 56%) compared to non-FSGS adolescents (77%) (p < 0.001) and was not significantly different from CD graft survival in FSGS (51%) or non-FSGS groups (61%). The relative risk (RR) of graft failure was greatest in LD transplant with FSGS (RR = 1.75; p < 0.001), compared to LD transplants without FSGS (RR = 1.0). Recurrent primary disease accounted for 15.2% of all graft failures in adolescents transplanted for FSGS with no difference between LD (17%) or CD (13.8%) grafts. Recurrent disease accounted for 3.2% of graft failures in adolescents without FSGS. Recurrent disease was the only cause of graft failure that differed between groups (p < 0.001). When compared to patients up to age 12 yr with FSGS, graft survival in both LD and CD transplants was worse in adolescents with FSGS (LD p = 0.035, CD p < 0.001). In conclusion, FSGS has a negative impact on graft survival in adolescents. Recurrence of FSGS results in a loss of the expected LD graft survival advantage in adolescents. Furthermore, adolescents with FSGS have decreased graft survival compared to younger children with FSGS. These data suggest that the rationale for LD transplantation in adolescents with FSGS should be based on factors other than the increased graft survival typically seen with LD transplantation.