The purpose of the current study was to conduct a large-scale, geographically diverse comparison of health risk behaviors between a broad range of sexual orientation and gender identity groups to more fully understand the health risks of subgroups within the LGBT community. A total of 3,279 individuals self-identifying as LGBT (e.g., lesbian, gay, bisexual, pansexual, transgender, genderqueer, and/or another gender or sexual minority) were recruited from across the United States through 2 sequentially implemented online recruitment methods. Participants completed a demographic assessment and the Health Risk Questionnaire (assessing diet and exercise, substance use and smoking, motor vehicle risks, sexual behaviors, violence, and medical risk-taking). Significant differences were found across genders for 18 of the 28 health risk behaviors investigated and across sexual orientations for 23 behaviors. Major differences emerged particularly with relation to diet and exercise behaviors, as well as sexual risk-taking, substance use, and medical risk-taking. Groups with notably elevated health risk behaviors included transgender women (diet and exercise behaviors), cisgender men (alcohol-related risk-taking), bisexual participants (substance use), and both transgender men and pansexual participants (self-harm). Differences between transgender participants and genderqueer or nonbinary participants were stark, indicating that these frequently combined groups have distinct health risk profiles. Results suggest that there are extensive and largely variable levels of engagement in health risk behaviors within the LGBT community. In addition, gender and sexual orientation subcategories that are traditionally collapsed into 1 category (i.e., transgender and bisexual) evidenced strikingly different risks when examined independently. Recommendations for future research and LGBT health promotion efforts are discussed.