<p>The Data Distribution Service (DDS) is a middleware protocol designed for real-time distributed systems and is increasingly used in healthcare to support efficient, scalable communication. Its Security Plugins Interface (SPI) enhances data protection by enabling customizable Quality of Service (QoS) security policies. However, deploying DDS in real-time medical environments poses challenges due to the stringent requirements for both low latency and high data protection. The SPI’s flexible configuration options can be complex, increasing the risk of misconfiguration and potential vulnerabilities. Moreover, existing DDS Security Plugins provide limited empirical validation for medical data protection, and comparative studies on their performance remain scarce. This study addresses the gap by simulating a real-time medical communication environment using RTI Connext Secure and the MetaCares Monitoring Station. The performance of DDS Security Plugins was evaluated under multiple threat scenarios—unauthorized domain access, tampering, and replay attacks. Results show that these plugins effectively mitigate such threats while maintaining acceptable system responsiveness, introducing an additional 0.05–0.25&#xa0;s of latency (after subtracting the baseline 36.85 ms) without noticeable degradation. This provides the first empirical comparison of DDS SPI configurations across security modes, highlighting the trade-offs between protection and performance in real-time medical data exchange. However, further validation under broader clinical datasets and operational conditions is necessary to generalize these findings for production-scale healthcare systems.</p>