Respondent-driven sampling (RDS) was used to conduct a biobehavioral survey among men who have sex with men (MSM) in three cities in the Republic of Panama. We estimated the prevalence of HIV, syphilis, and other sexually transmitted infections (STIs), sociodemographic characteristics, and sexual risk behaviors. Among 603 MSM recruited, RDS-adjusted seroprevalences (95 % confidence intervals) were: HIV-David 6.6 % (2.2-11.4 %), Panama 29.4 % (19.7-39.7 %), and Colon 32.6 % (18.0-47.8 %); active syphilis-David 16.0 % (8.9-24.2 %), Panama 24.7 % (16.7-32.9 %), Colon 31.6 % (14.8-47.5 %); resolved HBV infection-David 10.0 % (4.8-16.8 %), Panama 29.4 % (20.0-38.3 %), and Colon 40.6 % (21.9-54.4 %); herpes simplex virus type 2-David 38.4 % (27.9-48.9 %), Panama 62.6 % (52.8-71.0 %), and Colon 72.9 % (57.4-85.8 %). At least a third of MSM in each city self-identified as heterosexual or bisexual. HIV prevalence is concentrated among MSM. Preventive interventions should focus on increasing HIV and syphilis testing, and increasing promotion of condom awareness and use.