Background: Massive transfusion protocols (MTP) are widely used to rapidly deliver blood products to bleeding trauma patients. Every minute delay in blood product administration in bleeding trauma patients is associated with a 5% increased odds of death. In-situ simulation (ISS) is simulation that takes place in the actual clinical work environment. We used ISS as a novel, prospective and iterative quality improvement (QI) approach to identify and improve MTP steps that impact time to blood delivery (TTBD) during actual trauma resuscitations. Aim Statement: To reduce the TTBD for bleeding trauma patients by 20% over a 12-month ISS-based QI initiative. Measures & Design: We conducted twelve high-fidelity, interprofessional ISS sessions at a Level-1 trauma center in Toronto, Canada. We used clinician video review as well as extensive stakeholder involvement, including with nurses, porters, blood bank and human factors experts, to develop Plan-Do-Study-Act (PDSA) cycles for MTP improvement. Our three major PDSA cycles revolved around: 1) decreasing MTP activation time; 2) reducing the unpredictable and inefficient transport times for the blood itself; and 3) improving the notification of blood product arrival in the trauma bay. Each PDSA cycle was iteratively tested with ISS prior to implementation into clinical care. Outcome measure was the mean TTBD for trauma patients requiring MTP (in minutes, standard deviation [SD]). Process measures included time to MTP activation and porter transport times. Balancing measures included stakeholder satisfaction. Evaluation/Results: Our baseline TTBD for MTP patients was 11.58min (n = 41, SD 6.8). There were 54 trauma patients that had MTP during the ISS-based QI initiative, and their mean TTBD was 10.44min (SD 6.1). The TTBD after the QI initiative was 9.12min, sustained over 1 year (n = 50, SD 5.3; 21.2% relative reduction, p < 0.05). A run chart did not show special cause variation chronologically related to our interventions. Patients in each group were similar in demographic data, trauma characteristics and injury severity score. Discussion/Impact: We achieved a 21.2% reduction in TTBD for trauma patients requiring MTP with an ISS-based QI initiative. ISS represents a novel approach to the identification and iterative testing of process improvements within trauma care. This methodology can and should be included in QI projects in order to safely test and improve processes of care before they impact real patients.