Young men who have sex with men account for approximately 20% of incident HIV infections in the U.S. Antiretroviral pre-exposure prophylaxis (PrEP) administered as a daily pill has been shown to decrease HIV acquisition in at-risk individuals. New modalities for PrEP are being developed and tested, including injectable PrEP; however, acceptability of these emerging modalities has not yet been examined in youth. We conducted six focus groups with 36 young men and transgender men and women who have sex with men in Boston, Chicago, and Los Angeles in 2016 to assess interest in and preference for different PrEP modalities. Youth were purposively recruited based on diversity of age, race/ethnicity, and prior PrEP experience. Data were coded using content coding based on key domains of the interview guide, in particular around the central themes of interest in and barriers and facilitators to injectable PrEP use. Participants were knowledgeable about oral PrEP but suggested barriers to broader uptake, including stigma, marginalization, and access to information. While participants were split on preference for injectable versus oral PrEP, they agreed quarterly injections may be more manageable and better for those who have adherence difficulties and for those who engage in sex more frequently. Concerns specific to injectable PrEP included: severity/duration of side effects, pain, level of protection prior to next injection, distrust of medical system and injections, and cost. Understanding barriers to and preferences for diverse prevention modalities will allow for more HIV prevention options, improved products, and better interventions, thus allowing individuals to make informed HIV prevention choices.