This study examined victimisation, substance misuse, relationships, sexual activity, mental health difficulties and suicidal behaviour among adolescents with sexual orientation concerns in comparison to those without such concerns. 1112 Irish students (mean age 14yrs) in 17 mixed-gender secondary schools completed a self-report questionnaire with standardised scales and measures of psychosocial difficulties. 58 students (5%) reported having concerns regarding their sexual orientation. Compared with their peers, they had higher levels of mental health difficulties and a markedly-increased prevalence of attempted suicide (29% vs. 2%), physical assault (40% vs. 8%), sexual assault (16% vs. 1%) and substance misuse. Almost all those (90%) with sexual orientation concerns reported having had sex compared to just 4% of their peers. These results highlight the significant difficulties associated with sexual orientation concerns in adolescents in Ireland. Early and targeted interventions are essential to address their needs.