Since usability is considered a significant success factor for Clinical decision support systems (CDSSs), this study seeks to assess the usability of an electronic medical records-embedded CDSS for arterial blood gas (ABG) interpretation and ordering. The current study was conducted in the general ICU of a teaching hospital, using the System Usability Scale (SUS) and interviews with all anesthesiology residents and intensive care fellows in two rounds of CDSS usability testing. The feedback from the participants was discussed with the research team across a series of meetings, and the second version of CDSS was designed and tailored to participants’ feedbacks. Subsequently, the CDSS usability score increased from 67.22±4.58 to 80.00±4.84 (P-value<0.001) through participatory, iterative design and the users’ usability testing feedbacks.