Background Men who have sex with men (MSM) and transgender women (TW) in Peru bear a disproportionate burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). In a context of quickly expanding communication technology, increasing numbers of MSM and TW are using social media applications to seek sex partners. Understanding social media users and their sex partnering practices is needed to update HIV and STI prevention programming. Methods In Lima, Peru, 312 MSM and 89 TW from 2 STI clinics underwent HIV and STI testing and participated in a survey of demographics, behaviors, sexual health, and social media practices. χ 2, t tests, and Wilcoxon Mann-Whitney tests were used to compare those with and without recent social media sex partners. Results Men who have sex with men with social media sex partners were younger, more educated, and more likely to identify as gay. They were significantly more likely to report greater numbers of sex partners, including anonymous sex partners; sex in higher-risk venues, orgies, and have rectal Neisseria gonorrhoeae or Chlamydia trachomatis infection. Transgender women with social media sex partners were also younger, more likely to participate in sex work, and have a lower rate of rapid plasma reagin positivity or history of syphilis. Participants reported using several social media sites including sexual hook-up applications, websites for gay men, pornographic websites, and chat sites, but the most common was Facebook. Conclusions Prevention strategies targeting Peruvian MSM and TW who use social media are needed to address higher-risk sexual behavior and the high burden of STIs.