Objectives Open-source Electronic Health Record (EHR) systems have gained importance. The main aim of our research is to guide organizational choice by comparing the features, functionality, and user-facing system performance of the five most popular open-source EHR systems. Methods We performed qualitative content analysis with a directed approach on recently published literature (2012–2017) to develop an integrated set of criteria to compare the EHR systems. The functional criteria are an integration of the literature, meaningful use criteria, and the Institute of Medicine's functional requirements of EHR, whereas the user-facing system performance is based on the time required to perform basic tasks within the EHR system. Results Based on the Alexa web ranking and Google Trends, the five most popular EHR systems at the time of our study were OSHERA VistA, GNU Health, the Open Medical Record System (OpenMRS), Open Electronic Medical Record (OpenEMR), and OpenEHR. We also found the trends in popularity of the EHR systems and the locations where they were more popular than others. OpenEMR met all the 32 functional criteria, OSHERA VistA met 28, OpenMRS met 12 fully and 11 partially, OpenEHR-based EHR met 10 fully and 3 partially, and GNU Health met the least with only 10 criteria fully and 2 partially. Conclusions Based on our functional criteria, OpenEMR is the most promising EHR system, closely followed by VistA. With regards to user-facing system performance, OpenMRS has superior performance in comparison to OpenEMR.