BACKGROUND We prospectively studied outcomes of sex reassignment, potential differences between subgroups of transsexuals, and predictors of treatment course and outcome. METHOD Altogether 325 consecutive adolescent and adult applicants for sex reassignment participated: 222 started hormone treatment, 103 did not; 188 completed and 34 dropped out of treatment. Only data of the 162 adults were used to evaluate treatment. Results between subgroups were compared to determine post-operative differences. Adults and adolescents were included to study predictors of treatment course and outcome. Results were statistically analysed with logistic regression and multiple linear regression analyses. RESULTS After treatment the group was no longer gender dysphoric. The vast majority functioned quite well psychologically, socially and sexually. Two non-homosexual male-to-female transsexuals expressed regrets. Post-operatively, female-to-male and homosexual transsexuals functioned better in many respects than male-to-female and non-homosexual transsexuals. Eligibility for treatment was largely based upon gender dysphoria, psychological stability, and physical appearance. Male-to-female transsexuals with more psychopathology and cross-gender symptoms in childhood, yet less gender dysphoria at application, were more likely to drop out prematurely. Non-homosexual applicants with much psychopathology and body dissatisfaction reported the worst post-operative outcomes. CONCLUSIONS The results substantiate previous conclusions that sex reassignment is effective. Still, clinicians need to be alert for non-homosexual male-to-females with unfavourable psychological functioning and physical appearance and inconsistent gender dysphoria reports, as these are risk factors for dropping out and poor post-operative results. If they are considered eligible, they may require additional therapeutic guidance during or even after treatment.