Background <p>The World Health Organisation’s “Test, Treat, and Track” initiative for malaria underscores the need for accurate diagnosis to guide effective treatment and reduce drug misuse. In Ghana, about 74% of malaria testing relies on rapid diagnostic test (RDT) kits, including the MERISCREEN Malaria Pf HRP-II Ag^® test, supplied through the Central Medical Stores. However, field performance can be influenced by factors such as antigen persistence, gene deletions, storage conditions, and user handling. This study evaluated the diagnostic accuracy and operational performance of the MERISCREEN Malaria Pf HRP-II Ag^® RDT in public health facilities within Nandom Municipality of Ghana.</p> Methods <p>A facility-based cross-sectional study was conducted in six health facilities from 1 to 31st July 2024. A total of 404 children under five years were recruited using systematic sampling. Blood samples were collected and tested for malaria parasite using both the microscope and RDT (MERISCREEN Malaria Pf HRP-II Ag^®) kit methods. Test validity parameters, including sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy, were calculated and the results were presented in a graph and tables.</p> Results <p>The sensitivity and specificity of the mRDT were 98.1 (95% CI 92.6–99.7) and 92.6% (95% CI 88.9–95.2), respectively, with PPV and NPV being 82.4% (95% CI 75.8–87.5) and 99.1% (95% CI 96.6–99.8), respectively. The overall accuracy of the MERISCREEN Pf HRP-II test kit was 94.8%.</p> Conclusion <p>The real-world performance parameters observed for the RDT kits were marginally lower than manufacturer-reported values. With an overall accuracy of nearly 95%, test outcomes of prequalified RDT kits can be deemed reliable for guiding malaria treatment in areas lacking microscopy services. However, strict adherence to storage guidelines, continuous user training, and periodic quality assessments are essential to maintain kit performance.</p>