Patient monitoring systems have evolved over the past decade as an important first-line monitoring and warning tool. The healthcare delivery is moderately shifting from the traditional manual process to computer-based electronic healthcare system, supported by advanced tools and technologies. Mobile healthcare applications are now increasingly integrating into the healthcare mainstream to provide mobility with patient’s electronic health record. However, the use of mobile raises the challenge of accuracy, stability, security and dependency of such applications in clinical care settings. In particular, lack of clinician engagement, poor user experience, and no clinical decision support are posing some serious issues on the acceptability of smartphone applications in clinical settings. The main aim of this research project was to develop a vital signs monitoring and decision support application for the clinician-as-a-user. An Android-based smartphone application has been developed to monitor vital signs on a mobile device in real-time and to provide rich decision support to the clinicians. The application is fully integrated with wireless medical devices for real-time vital signs monitoring and decision support backed by the six screens (6S) user experience framework for the smartphone applications in healthcare settings. The unique features and contributions that this research project provides are: (1) The ability to access, share, monitor, contact and stay connected with patient’s data anywhere; (2) Hospital-grade medical device connectivity using the standard Bluetooth protocol; (3) Rich clinical decision support in real-time based on the patient’s recent vital signs (health data); (4) The ‘6S’ framework developed for clinician-centered mobile user experience by adapting the international standards and protocols. The proposed application has been evaluated using the best-practice guidelines for a successful mobile healthcare application. The criteria include review of the market available applications, literature review of best-practice guidelines, user engagement, privacy and security and standard design architecture for medical device integration. The proposed application demonstrates the easy to use screens and unique functionality including; patient list with search options, real-time viewing of vital signs, integrated medical devices, structured data entry, historic data, evidence-based knowledgebase search, clinical notes and clinical decision support via clinical risk assessments tools, scales and scores. The proposed smartphone-based clinical decision support application could be seen as a potential standard/ best-practice tool that will help the clinicians to deliver better and timely outcomes. The functional design and implementation required rigorous and systematic workflow methodologies to be acceptable in the clinical care settings. The patient-orientated workflow and the available automated clinical assessment tools and calculators can assist researchers with collecting data that can help clinicians in future decision making.