: HIV/AIDS prevention has historically encountered many obstacles. Understanding the factors affecting HIV/AIDS prevention is central to designing and implementing suitable context-specific interventions. Research relating to HIV prevention in the Middle East and North African region is required to address the gradually increasing HIV epidemic. : This study aimed to explore the perspectives of employees/health care professionals who are working or have worked within HIV prevention in Sudan and Yemen on the challenges and facilitating factors facing HIV prevention. : A qualitative approach was employed using an open-ended questionnaire. Sixteen stakeholders from governmental and non-governmental agencies participated in the study. The questionnaire focused on the various challenges and facilitating factors facing HIV prevention as well as proposed possible solutions from the perspectives of the participants. The data were analysed using thematic analysis. : The study illustrated the similarities in context and HIV prevention systems between Sudan and Yemen. Thematic analysis resulted in three main themes: I) much is achieved despite difficulties; II) a programme left to be paralysed; this theme addressed the main obstacles facing HIV prevention in Sudan and Yemen generating a total of six sub-themes; III) comprehensive change is needed. The participants drew focus and attention to vital changes required to improve the delivery of HIV prevention services. : Increased financial support for HIV prevention in Sudan and Yemen is urgently needed. De-stigmatisation and increased political support, advocacy and improved legislation for people living with HIV (PLHIV) are required for the sustainability and effectiveness of HIV prevention programmes in Sudan and Yemen. Civil society organisations must be aided and supported in their role in engaging key populations.