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ABSTRACT: Triggered by the COVID-19 crisis, Israel’s Ministry of Health (MoH) held a virtual datathon based on deidentified governmental data. Organized by a multidisciplinary committee, Israel’s research community was invited to offer insights to help solve COVID-19 policy challenges. The Datathon was designed to develop operationalizable data-driven models to address COVID-19 health policy challenges. Specific relevant challenges were defined and diverse, reliable, up-to-date, deidentified governmental datasets were extracted and tested. Secure remote-access research environments were established. Registration was open to all citizens. Around a third of the applicants were accepted, and they were teamed to balance areas of expertise and represent all sectors of the community. Anonymous surveys for participants and mentors were distributed to assess usefulness and points for improvement and retention for future datathons. The Datathon included 18 multidisciplinary teams, mentored by 20 data scientists, 6 epidemiologists, 5 presentation mentors, and 12 judges. The insights developed by the three winning teams are currently considered by the MoH as potential data science methods relevant for national policies. Based on participants’ feedback, the process for future data-driven regulatory responses for health crises was improved. Participants expressed increased trust in the MoH and readiness to work with the government on these or future projects.