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Intramuscular cabotegravir for long-acting injectable HIV pre-exposure prophylaxis (i.e., LAI-PrEP) was approved by the U.S. FDA in 2021. We sought to explore LAI-PrEP decision-making among a nationwide sample of young sexual minority men (YSMM) 17–24 years old. In 2020, HIV-negative/unknown YSMM (n = 41) who met CDC criteria for PrEP were recruited online to participate in synchronous online focus groups eliciting preferences and opinions about LAI-PrEP, as well as the impact of a potential self-administered option. Data were analyzed using inductive and deductive thematic analysis with constant comparison. Preferences and decision-making about LAI-PrEP varied widely among YSMM, with participants frequently comparing LAI-PrEP to oral PrEP regimens. We identified five key themes related to LAI-PrEP decision-making including concerns about adherence to PrEP dosing and clinic appointments, awareness and knowledge of PrEP safety and efficacy data, comfort with needles, minimizing PrEP stigma, and considerations of self-administration. YSMM acknowledged more PrEP options as beneficial to supporting uptake and persistence.