Pre-exposure prophylaxis (PrEP) is one of the best biomedical HIV prevention tools available. However, uptake, particularly in communities of men who have sex with men (MSM) and transgender individuals assigned male at birth (AMAB), remains low. Further, the role of an individual's social support structure on PrEP uptake and adherence remains largely understudied. Understanding MSM and AMAB transgender individuals' perceptions of PrEP use as well as support and patterns of disclosure of (or intent to disclose) their PrEP status may offer key insights into how best to improve uptake in vulnerable communities. Further, the influence of one's social connections on other factors, such as perceptions of and conversations about PrEP deserves attention as well, as these factors may be key to improved knowledge and uptake. Therefore, we assessed perceptions of PrEP use, disclosure of or intent to disclose PrEP status, and social support and associated factors among a cohort of MSM and AMAB transgender individuals in a large Midwestern city. Results demonstrated that, among those not taking PrEP, bisexual participants and those unsure of their sexual identity were less likely to be comfortable with the idea of disclosing PrEP use were they ever to start taking it. Encouragingly however, we found that individuals who reported disclosing their PrEP status had high rates of support among friends and relatives. We also observed that knowing someone else who was on PrEP was associated with increased likelihood of discussing PrEP with one's medical provider, as was increased age. Other findings and implications for research, policy, and practice are discussed within.