The aim of this study was to identify vulnerability to HIV among transsexual women and transvestites. Cross-sectional, quantitative-qualitative study carried out in northeastern Brazil. A virtual questionnaire and a semi-structured interview script were used for data collection among transsexual women and transvestites aged 18 years or older, with access to a messaging application and/or e-mail. The participants’ were recruited using the snowball technique. Descriptive analysis was carried out to characterize the participants, and qualitative data were processed using Content Analysis. Of the total of 72 participants, 04 participants reported being HIV-positive and 12 granted an interview. The following vulnerability markers were identified: inconsistent condom use; difficulty in negotiating condom use with sexual partners; difficulty in accessing health services, especially in situations of symbolic violence, such as not using the social name or pronoun errors; HIV stigma; and poor training of health professionals to deal with this population. The study population is characterized by young people with low level of schooling, showing vulnerabilities in the individual, social and programmatic dimensions. It is necessary to: improve access to health services; implement professional training programs since the undergraduate level in various areas of health; and develop more effective multidisciplinary approaches for this population.