MPH / Department of Public Health / HIV/AIDS is an overwhelming global pandemic that affects the country’s health-care system. In order to reduce HIV/AIDS morbidity and mortality, the World Health Organization has called on countries to provide earlier access to antiretroviral therapy. In order to comply with the World Health Organization’s call, South Africa has developed the National Consolidated Guidelines, which were aimed at increasing access to ART as well as reducing new infections through viral suppression. Although the new guidelines have been implemented, they have not been fully implemented, especially in rural-based Primary Health Care facilities. The researcher observed that women who were pregnant were not tested every three months, as prescribed by the HIV/AIDS guidelines. The aim of this study was to investigate Challenges faced by health professionals regarding the implementation of HIV/AIDS guidelines at PHC facilities of Vhembe District, South Africa. This study adopted a qualitative, explorative, descriptive and contextual approach targeting nurses working at rural-based primary health care facilities at Vhembe District. Face-to face in-depth, Semistructured interviews were conducted, audiotaped and transcribed verbatim. The study used non-probability quota sampling method to identify participants until data saturation was reached with 12 participants. The results revealed that nurses faced some challenges when implementing HIV/AIDS guidelines, including shortages of resources, poor technical support, poor infrastructure, work overload, patients starting ART while there are not ready, shortage of ART, late booking of antenatal care, and mothers’ denial of HIV positive status, HIV positive babies, and poor RPC after birth. Ethical considerations were observed throughout the study. The data collected was analyzed using interpretative phenomenological analysis and all measures to ensure trustworthiness of the study findings were ensured. Some recommendations were made based on the findings of the study / NRF