The introduction of the National Surveillance Centre (NSC) has improved the efficiency and effectiveness of managing medicines availability within the public healthcare system in South Africa. However, at present, there is limited data regarding the perceptions among users of the NSC and challenges that need addressing. A descriptive quantitative study was performed among all registered active NSC users between August and November 2022. Overall, 114/169 users responded to a custom-developed, self-administered questionnaire (67.5% response rate). Most respondents used the Stock Visibility System (SVS) National Department of Health (NDoH) (66.7% for medicines and 51.8% for personal protective equipment (PPE) or SVS COVID-19 (64.9% for COVID-19 vaccines) or RxSolution (57.0% manual report or 42.1% application programming interface (API)) for reporting medicines, PPE, and COVID-19 vaccines to the NSC and were confident in the accuracy of the reported data. Most respondents focused on both medicines availability and reporting compliance when accessing the NSC, with the integrated medicines availability dashboard and the COVID-19 vaccine dashboard being the most popular. The respondents believed the NSC allowed ease of access to data and improved data quality to better monitor medicines availability and use. Identified areas for improvement included improving internet connectivity, retraining some users, standardising the dashboards, adding more data points and reports, and expanding user adoption by increasing licence limits. Overall, this study found that the NSC in South Africa provides an effective solution for monitoring and improving medicines availability.