Objective: The syndemics framework has been used to explain the high rates of HIV infection among gay and bisexual men. However, most studies have relied primarily on urban or otherwise limited (e.g., single location) samples. We evaluated the prevalence of syndemics—here, depression, polydrug use, childhood sexual abuse, intimate partner violence, and sexual compulsivity—among gay and bisexual men from across the United States, including nonurban areas. Method: Using data from a national sample of 1,033 HIV-negative gay and bisexual men, demographic differences in the prevalence of each syndemic condition and associations with HIV transmission risk behavior were examined. Results: More than 62% of men reported at least 1 syndemic condition. Prevalence did not vary by U.S. region—however, a larger proportion of nonurban men and those with lower income and education levels were above the median number of syndemic conditions. In bivariate analyses, HIV transmission risk behavior was associated with each syndemic condition except for childhood sexual abuse, whereas in multivariate analyses, it was associated with polydrug use, sexual compulsivity, being Latino, and being single and was highest among those reporting 3 or more syndemic conditions. Conclusions: Rates of syndemic conditions among this national sample of gay and bisexual men were generally comparable to previous studies, however elevated rates in nonurban men suggest the need for targeted intervention and support. Links observed between syndemics and HIV transmission risk behavior highlight the ongoing need to address psychosocial concerns among gay and bisexual men in order to reduce their disproportionately high rates of HIV infection.