In 2010, men who have sex with men (MSM) represented 4% of the population in the United States (US) and accounted for 78% of all new Human Immunodeficiency Virus (HIV) infections among Hispanic men. Hispanic men who have sex with men (HMSM) accounted for the third largest number of new HIV infections (6,700 cases). This dissertation explored the effects of age, loneliness, substance use, depression, and social support on high risk sexual behaviors that predispose middle aged HMSM to sexually transmitted infections (STIs) and HIV infection risk. A sample of 150 urban HMSM aged 40 to 65 were surveyed in this study. Singer’s Syndemics Theory (1996) provided this study’s theoretical framework. Data was analyzed using a variety of parametric and non-parametric statistics. Loneliness, social support, depressive symptoms, alcohol/drug use, and sexual risk behaviors were found to have an influence on HIV infection status in this study. Partner status, religious affiliation and age did have an influence on alcohol use in this study’s participants. Also, participants with increased age had increased depressive symptoms in this study. Lastly, depressive symptoms, substance use, social support, and loneliness did have an influence on sexual risk behaviors in this study’s participants, specifically alcohol use and illicit drug use. The findings from this study should be used to assess, diagnose, plan, implement and evaluate prevention strategies geared to reduce STI and HIV infection in this population. Future research should build on these findings and develop tailored risk reduction interventions addressing HMSM, with particular attention to the understudied age group of the middle aged HMSM.