The international healthcare systems interoperability is an unresolved technological area at the moment. This paper demonstrates the results of the software engineering research for simplex syntactic and semantic technical interoperability of hospital information systems, eHealth smart device technology and clinical telemedicine instruments through the recently developed Telemedicine Interoperability Hub. Several similar experiments exist. This research is unique in building a prototype interconnecting not only healthcare information systems with each other, but aiming to establish a general healthcare interoperability scheme including also the eHealth smart devices and telemedicine instruments. The aim of this research is to establish cloud-based data interchange capability with the newly developed information technology system interconnected with the emerging eHealth Internet of Things solutions and the classical hospital information system architecture. Notwithstanding the international information technology medical data exchange standards, like Health Level Seven, the adoption of an industry-wide open telemedicine syntactic and semantic interoperability standard is necessary. The research studied varying simplex, duplex, full-duplex, data package- and file-based information technology modalities establishing stable system interconnection among clinical instruments, healthcare systems and eHealth smart devices. This research is the manifestation of the trilateral cooperation of the University of Debrecen Department of Information Technology, Semmelweis University Second Paediatric Clinic and T-Systems Healthcare Competence Center Central and Eastern Europe. The developed experimental software engineering solution was embedded in hybrid cloud architecture after testing private cloud Infrastructure-as-a-Service and Public Cloud Software-as-a-Service technical solutions.