Background Men in Uganda contribute significantly to new HIV infections annually yet PrEP uptake among them is low and those initiated are likely to discontinue usage. We explored the barriers and facilitators to PrEP uptake among high-risk men employed in private security services with negative HIV results after testing at workplaces in Uganda. Methods An explorative qualitative study comprising in-depth participant interviews. Data were collected via telephone calls and manually analyzed by inductive content analysis. Results Fifty-six (56) men participated, 27(48.21%) had heard about PrEP, and 29(51.79%) were willing to initiate it. Four categories emerged for the facilitators of PrEP uptake including the perceived need for HIV prevention, awareness creation, availability, and sexual freedom. Six categories emerged for the barriers to PrEP uptake. These were: Inaccessibility of PrEP services, Misinformation, Knowledge deficit, Medication-related barriers, Potential for increased risky sexual behavior, and Perceptions about PrEP use. Conclusion The findings suggest the need for healthcare providers to offer information regarding PrEP and HIV prevention services and mass sensitization campaigns to facilitate uptake. Participants recommend mass roll-out of PrEP to lower-level facilities and accessible pick-up points for men such as workplaces. The men also suggested the use of longer-acting PrEP modalities such as an injectable option or an option that is utilized specifically by the female partner. Finally, the stigma surrounding PrEP use could be reduced by the separation of PrEP and ART services at health facilities, or special pick-up days to reduce waiting times.