Abstract Introduction End‐user perspectives are vital to the design of new biomedical HIV prevention products. Conjoint analysis can support the integration of end‐user perspectives by examining their preferences of potential pre‐exposure prophylaxis (PrEP) products. The Microbicides Trial Network (MTN) 035 protocol examined three placebo rectal dosage forms (insert, enema and suppository) that could deliver PrEP prior to receptive anal sex (RAS). Methods Between April 2019 and July 2020, we enrolled 217 HIV‐negative, cisgender men who have sex with men (MSM; n = 172; 79.3%) and transgender people (n = 47; 20.7%) ages 18–35 into a randomized cross‐over trial across Malawi, Peru, South Africa, Thailand and the United States. Participants used each product prior to RAS over 4‐week periods. Participants completed a conjoint experiment where they selected between random profiles using seven features (dosage form, timing of use before sex, side effects, duration of protection, effectiveness, frequency of use and need for a prescription). Results Effectiveness was the strongest determinant of choice (30.4%), followed by modality (18.0%), potential side effects (17.2%), frequency of use (10.8%), duration of protection (10.4%), timing of use before sex (7.4%) and need for a prescription (5.9%). Relative utility scores indicated that the most desirable combination of attributes was a product with 95% efficacy, used 30 minutes before sex, offering a 3‐ to 5‐day protection window, used weekly, having no side effects, in the form of an enema and available over‐the‐counter. Conclusions Choice in next‐generation PrEP products is highly desired by MSM and transgender people, as no one‐size‐fits‐all approach satisfies all the preferences. MTN‐035 participants weighed product features differently, recognizing the need for diverse, behaviourally congruent biomedical options that fit the needs of intended end‐users.