Objective: SPARX is a form of computerized cognitive behavioural therapy in serious game format funded via the Ministry of Health to be freely available in New Zealand. At registration users identify themselves as male, female, transgender or intersex. We aimed to establish whether adolescent transgender users of SPARX, compared to adolescent male and female users, were more likely to have high mental health needs at baseline and were more likely to complete SPARX. We also sought to determine changes in transgender adolescents’ depressive symptoms after using SPARX. Methods: Quantitative analysis of 5 years of usage data from the nation-wide delivery of SPARX in New Zealand. Results: There were 9079 adolescents who completed the registration process and used SPARX, 2.3% (n = 207) identified as transgender. The majority of transgender registrants (69.0%) completing a baseline Patient Health Questionnaire – modified for Adolescents were categorized as having high mental health needs, significantly more so than male and female registrants (p < 0.001). Over half of all SPARX registrants completed the first module of the program, with subsequently lower proportions of transgender registrants completing Module 4 (p = 0.005) and Module 7 (i.e. the last module, p = 0.048). Of those registrants completing a baseline and subsequent Patient Health Questionnaire – modified for Adolescents, both male (n = 247) and female (n = 630) registrants, on average, had improvements in their scores (2.68 and 3.15, respectively), whereas transgender registrants (n = 14) did not (−0.43) (p = 0.048). Conclusion: This is the first study describing the impact of an e-therapy on transgender young people. The analysis of data from this free self-help intervention suggests that transgender adolescents seeking treatment for depression have particularly high mental health needs, and an existing well tested tool may be less effective for them than it is for others. Taken together the results appear to suggest targeted efforts may be required for transgender adolescents.