The lesbian, gay, bisexual, and transgender (LGBT) communities in the United States are disproportionately impacted by smoking, including incidence rates and a lower rate of cessation success. Previous studies have shown that the emotional impact of social stigma and discrimination have contributed to this pronounced health disparity. Utilising data from three years of quitline callers receiving cessation treatment from National Jewish Health, we examine how LGBT callers differ from straight/heterosexual callers in terms of demographic characteristics, tobacco use history, and the prevalence and consequences of emotional or mental health problems. Findings suggest that the LGBT population begins using tobacco in pre-adolescence at a much higher rate than other quitline callers. The most striking finding is that the LGBT callers report higher rates of mental health issues than other callers. In addition, these individuals feel that their mental health issues negatively impact their ability to have a successful quit attempt. This study contributes to the broader understanding of factors associated with elevated rates of tobacco use in the LGBT community, which may inform potential specialised prevention and cessation efforts for this high-risk population.