Objective: In prehospital helicopter emergency medical service (HEMS) settings, the medical team has limited monitoring options, usually restricted to systemic variables. Regional tissue oxygenation (rO2) can be assessed by near-infrared spectroscopy (NIRS), but clinical NIRS monitors are unpractical (“big boxes” and additional cables) in HEMS. As an alternative, we identified a wearable, athlete training NIRS device (Moxy; Idiag, Fehraltorf, Switzerland) and hypothesized that it would be applicable in our HEMS setting. Methods: This feasibility study was performed at the Dutch HEMS Lifeliner 1. The Moxy sensor was tested in-flight and on ground. We tested various anatomic measurement spots, and multiple conditions and interventions were imposed to track rO2. Results: The rO2 measurements with the wearable Moxy NIRS device are both feasible and practical in an HEMS setting. Multiple conditions and interventions were tested successfully (eg, tourniquet placement [rO2↓], muscle compression [rO2↓], reperfusion [rO2↑], oxygen administration [rO2↑], hyperemia [rO2↑], and venous congestion [rO2↓]). Conclusion: Our results suggest that rO2 measurements with the wearable Moxy NIRS device are both feasible and practical in HEMS, and Moxy allows the tracking of simulated pathophysiologic effects on rO2. Future studies will have to verify our preliminary data and elucidate if and how wearable NIRS monitoring may support treatment in HEMS and improve patient outcome.