Abstract Objectives Ventilator management in prehospital settings using end-tidal CO₂ can lead to inappropriate ventilation in the absence of point of care blood gas (POCBG) measurements. Implementation of POCBG testing in helicopter Emergency Medical Services (HEMS) is limited in part because of concern for preanalytical and analytical errors due to altitude, vibration, and other associated environmental factors and due to insufficient documentation of implementation challenges. Methods We performed accuracy and precision verification studies using standard materials tested pre-, in-, and post-flight (n=10) in a large HEMS agency. Quality assurance error log data were extracted and summarized for common POCBG errors during the first 31 months of use and air medical transport personnel were surveyed regarding POCBG use (n=63). Results No clinically significant differences were found between pre-, in-, and post-flight blood gas measurements. Error log data demonstrated a reduction in device errors over time. Survey participants found troubleshooting device errors and learning new clinical processes to be the largest barriers to implementation. Continued challenges for participants coincided with error log data including temperature and sampling difficulties. Survey participants indicated that POCBG testing improved patient management. Conclusions POCBG testing does not appear to be compromised by the HEMS environment. Temperature excursions can be reduced by use of insulated transport bags with heating and cooling packs. Availability of POCBG results in air medical transport appeared to improve ventilator management, increase recognition of ventilation-perfusion mismatch, and improve patient tolerance of ventilation.