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Pre-exposure prophylaxis (PrEP) is a highly effective biomedical prevention strategy that remarkably reduces HIV transmission risk. Although PrEP has been available in Nepal since 2019, very little is known about PrEP use among MSM in Nepal. This study aimed to examine PrEP awareness and its use among Nepali MSM and the factors influencing its adoption. A cross-sectional survey was conducted among MSM in Nepal between October and December 2022 (N = 250). Bivariate analysis and logistic regression were performed to determine factors associated with awareness and use of PrEP. In the study population, 59.6% of participants were aware of PrEP, however, only 30.4% of them had utilized it. The odds of PrEP awareness were higher among participants who had completed high school or above (aOR = 4.1; 95% CI = 1.8–9.6), those with health insurance coverage (aOR = 6.9; 95% CI = 2.1–22.3) and had tested for HIV (aOR = 21.2; 95% CI = 8.3–53.9). Similarly, participants who identified as gay (aOR = 3.4; 95% CI = 1.4–8.4), had visited a doctor within the past 6 months (aOR = 2.9; 95% CI = 1.2–6.5), had previously tested for HIV (aOR = 12.3; 95% CI = 3.4–44.7), and had been diagnosed with sexually transmitted infections (aOR = 7.0; 95% CI = 2.5–19.5) were more likely to have used PrEP. Our results highlight the critical importance of healthcare providers engaging in providing care for MSM, including facilitating as well as discussions about PrEP. In addition, there is a pressing need for innovative strategies (e.g., peer educators, social media, online facilitating technologies) to disseminate PrEP knowledge and reduce stigma surrounding PrEP. [ABSTRACT FROM AUTHOR]