This article was migrated. The article was marked as recommended. Background: Holistic nursing of intensive care unit (ICU) patients encompasses diverse challenges requiring regular in situ evaluation, training and assessment. Simulation has been adopted as a research and training tool in medicine; however, evidence for its use in enhancing holistic care at multi-sites is limited. Objective: This study aims to conduct a simulation-based research (SBR) at four ICU for standardized training of holistic nursing. Methods: There are stages of evaluating, training+in-training assessment and post-course assessment in this SBR. Specifically, the curriculum-mapped scenarios were developed according to the deficiency of each site after evaluating stage. At the training stage, the first simulation by team was defined as preparation step and the in-training assessment was undertaken at the second simulation. Results: From January 2017 to October 2018, sixty-four ICU nurses (16 teams, 4 teams in each site) at RCU, PICU, NICU and GYN ICU, attend 8 similar courses (2 courses at each site) over 20 months. In comparison with baseline performance, in-training assessments revealed the significant improvement of attendee's skills of holistic nursing. Attendees commented that simulation was a valuable training modality to enhance skills of holistic care including history taking, physical examination, communication and teamwork that are rarely taught among ICU nurses. Post-course workplace assessment by senior nurses revealed the high frequency of clinical application of holistic nursing by attendees. Additionally, post-course self assessment revealed a high attendee's confidence of holistic approaching in ICU. Conclusion: This pilot SBR demonstrated the feasibility of a standardized holistic care simulation program across four ICUs. In situ simulation and post-course workplace assessment affords situational learning without compromising patient safety and is an exciting and novel training of holistic nursing for ICU that could be integrated into regular intervention.