Pre-exposure prophylaxis (PrEP) uptake has been extremely low among key groups. PrEP-related stigma and shaming are potential barriers to uptake and retention in PrEP programs. There is a lack of literature describing PrEP stigma. In order to fill this gap, we recruited online 43 HIV-negative Men who have Sex with Men (MSM) who use PrEP. Semistructured interviews were conducted to explore their perceptions and experience of stigma related to PrEP use. Data were analyzed using Strauss and Corbin’s grounded theory and constant comparison techniques to enhance understanding of the lived experiences of MSM who use PrEP. The participants experienced PrEP stigma as rejection by potential/actual partners, stereotypes of promiscuity or chemsex, and labeling of both the user and the medication. They connected PrEP stigma with HIV stigma, generational differences, moralization of condom use, and inability to embrace one’s own sexuality. These findings point to a need to develop tailored interventions to address PrEP-related stigma and shaming for individuals, health-care professionals, and the MSM community-at-large.