Background: Performing CPR in EMS helicopters is difficult. Manual CPR presents a safety hazard because of the necessity to remove safety belts. Lack of a sterile cockpit (everyone and everything secured) during takeoff and landing, violates FAA regulations (FAR 135.100). The purpose of this trial was to evaluate survival before, and following, deployment of the LUCAS device in a helicopter EMS agency to assess its acceptability as a substitute for manual compressions. Methods: Patient care records from June 2009–September 2013 (pre-LUCAS) and October 2012–January 2016 (post-LUCAS) were identified. Demographics (age, sex), initial cardiac rhythm, patient outcome (survival to ED admission), and duration of in-flight CPR were abstracted. Basic comparisons of continuous variables were completed using unadjusted t-tests and unadjusted Chi-squared for categorical variables. Stratified ANOVAs were calculated to analyze the group differences in CPR time based on patient survival status prior to HEMS leaving the emergency department. Results: 109 runs (43 pre-LUCAS and 65 post-LUCAS) were abstracted. Gender (pre, 32% male vs. post, 68% male, p = 0.015) and initial rhythm (pre, 24% asystole vs. post, 76% asystole, p = 0.009) were significantly different between the study periods. There were no overall differences in age or survival (pre = 77% vs. post = 67%, p = 0.34) between the study periods. CPR was performed for a significantly longer period of time with the LUCAS compared to standard CPR (pre mean, 8.08 min (SD 7.58) vs. post mean, 14.66 min (SD 11.84), p = 0.0012). Despite the fact that CPRwas performed for a longer period of time with the LUCAS device, the percent of patients reported alive when HEMS left the ED was not different between the study periods (pre: F(2,44) = 2.01, p = 0.15, post: F(2,59) = 0.84, p = 0.44). Conclusions: There was no difference in survival to ED admission between the two compression methodologies. It appears the LUCAS device is clinically safe, and safer for the crew. In addition, the device allows the agency to be compliant with FAA regulations in the event of inflight cardiac arrests. This study is limited by its small sample size.