Adolescent girls and young women are disproportionately affected by HIV in many lower-resource settings. These individuals are often excluded from early clinical trials for new HIV prevention products, thus delaying potential access. We explored adolescent girls' and young women's (AGYW) perceptions of HIV risk, perspectives on trial participation, and understanding of research concepts. Individual or repeated in-depth interviews were conducted with a total of 43 AGYW. Interviews were conducted in participants' language of choice, audio-recorded, transcribed, and translated into English. Thematic analysis was applied. A total of 21 participants were enrolled from Dar es Salaam, Tanzania, and 22 from Pune, India. HIV risk perception varied by country, with Tanzanian participants often describing risk as behaviors tied to economic factors, and Indian participants describing risk as behaviors associated with limited HIV knowledge, inequitable gender norms, and pervasive sexual violence. Trial participation was largely viewed as acceptable; however, concerns were raised regarding standard recommendations for using condoms and contraception during trial participation, and the potential for side effects. Research concepts were notably challenging for participants to understand, particularly the concept of placebo. Although adult involvement was perceived as useful support in Tanzania, it was deemed essential for trial participation in India. Participants in our study described a need for and potential benefits of new HIV prevention products. Taking into consideration the local context, clinical trials with adolescent girls and young women should ensure understanding of research requirements and concepts, minimize preventive misconceptions, and consider involvement of a trusted adult.