There is limited information about sexual behavior among volunteers who participated in phase I/II human immunodeficiency virus (HIV) vaccine trial. This article describes the sexual behavior, practices before, and after participation in phase I/II HIV vaccine trial in Dar es Salaam, Tanzania. We conducted a qualitative descriptive study involving volunteers who participated in the phase I/II vaccine trial between 2007 and 2010. Purposeful sampling was used to recruit potential informants. Twenty-four in-depth interviews were conducted. The audio-recorded interviews were transcribed verbatim and analyzed using a thematic content analysis approach. The findings revealed that before participation in the HIV vaccine trial, informants were engaging in unprotected multiple sexual relationships. After the completion of the HIV vaccine trial, informants reported strengthened marital relationships, increased understanding of safer sexual practices, and HIV testing. However, the informants reported challenges regarding vaccine-induced seropositivity that adversely affected their sexual and marital relationships. Some informants re-engaged in risky sexual practices because they perceived the experimental vaccine was protective. The informants suggested having continued interventions within the community to enhance safer sexual practices. Participation in phase I/II HIV vaccine trials may positively and negatively influence changes in volunteers' sexual behaviors and practices. The trial interventions appear to improve compliance with safer sexual practices. However, the reported vaccine-induced seropositivity and the perception that experimental vaccines are protective need further appropriate interventions.