Introduction: Internationally mental distress is more prominent in the LGBTI community than the general population. The LGBTIreland study was set up to take stock of this in the Republic of Ireland. This paper reports on the analysis of the transgender group with reference to minority stress theory and cognitive dissonance theory. Method: An online survey was conducted addressing several aspects of mental health and distress that received responses from all groupings (n = 2,264) among which 12.3% (n = 279) identified as transgender. The survey consisted of several validated tools to measure depression, anxiety, stress (DASS-21), coping (CSES), self-esteem (RSES), alcohol and drugs misuse (AUDIT) and a variety of questions addressing demographics, experiential aspects, coping and self-related factors. Data analysis focused on predicting mental distress using DASS-general (composite of depression, anxiety and stress). Results: Transgender participants reported higher levels of mental distress, self-harm, suicidal ideation and attempts, and lower levels of self-esteem in comparison with the LGB groups, as well as the general population. Hierarchical multiple regression showed that 53% of variance in mental distress could be predicted from reduced self-esteem, the experience of harassment and not belonging in school. Furthermore, mental distress was highest among younger participants, those who were ‘not out’, those who had self-harmed and used avoidant coping. There was no significant difference in distress levels among those who had sought mental health support and those who had not. Conclusions: To understand mental distress in transgender people, the minority stress model is useful when taking into account both adverse external (environmental) and internal (cognitive/emotional) factors. The cognitive dissonance mechanism is essential in outlining the mechanism whereby gender incongruence is associated with psychological discomfort, low self-esteem and high mental distress.