BACKGROUND: Gender diverse people in Australia have higher levels of psychological stress, suicidal ideation and suicide attempts and have poorer self-reported health than cisgender people. OBJECTIVES: To determine if adults who experience gender incongruence have improved health-related quality of life and mental health with gender affirming treatment (hormone therapy and surgery), compared with no treatment. DATA SOURCES: PubMed, Web of Science, Embase and Psych Info. REVIEW METHODS: A systematic review of peer-reviewed publications in English from January 2010 to October 2022. Studies were included where: participants were treated with gender affirming surgery or hormone therapy for minimum 3 months and; validated patient reported outcome measures of health-related quality of life or mental health were reported. Quality of evidence assessment was undertaken using the Let Evidence Guide Every New Decision evaluation tool. RESULTS: Eighty-one publications were included for analysis. The systematic review indicated that there were significant improvements in the domains of mental illness, gender dysphoria, body image and health-related quality of life following gender affirming medical treatment as measured by a variety of patient reported outcomes. Meta-analysis showed significant improvement in body image (z = 4.47, P < 0.001) and health-related quality of life for psychological (z = 1.99, P = 0.047) and social relationships (z = 3.09, P = 0.002) following gender affirming surgery. CONCLUSIONS: There is evidence that hormones and surgery as a collective for adults with gender incongruence has therapeutic value and should be considered for funding within Australia's healthcare systems. The development and implementation of patient-reported outcome tools tailored for purpose (GENDER Q) will facilitate future research.