Background: Intraosseous (IO) pressure monitoring has not been explored as a potential invasive monitoring option for critically ill and injured patients. Objectives: The objective of this study was to describe IO pressure measurements in normal healthy volunteers. Methods: This is a prospective, proof of concept, pilot study of healthy volunteers approved by our local institutional review board. Inclusion criteria included age 18–70 year old, BMI 19–40, ability to provide informed consent, and no active treatment for any disease. Participants consented to have two IOs placed per device manufacturer recommendations (tibial and humeral). External cuff pressure readings were recorded every 5 min, and IO pressure measurements were recorded continuously for up to 60 min.A safety review committee reviewed data after the 10th and 15 participants were enrolled. Mean IO pressure readings and systolic/diastolic cuff pressure measures were summarized and are reported descriptively. The slopes of mean IO pressure readings from the start to the end of the monitoring session are also described. Results: Fifteen patients were enrolled between April and July 2015. Average patient age was 33 years old (range = 22–50), and 40% were female. The IO waveform morphology was arterial, including a distinct dichrotic notch. Respiratory variability within the waveform tracing was also observed in all subjects. Results from the humeral placements were inconsistent and are not presented. The median of the mean tibial IO pressure across the study sample was 60 mm Hg (IQR = 30.5–83.5 mm Hg). In the majority of participants, the mean tibial IO pressure was below the systolic and diastolic cuff readings. We observed a decrease in IO pressure from the initial placement until the final reading, with an approximate 1% decrease in pressure per minute. Conclusion: This is the first study in healthy volunteers establishing the presence of an intraosseous waveform, which was observed to be arterial in nature. The mean tibial IO pressure was consistently obtained but had a wide variation in absolute values. IO pressure decreased approximately 1% per minute during the testing period.