INTRODUCTION: It is difficult to obtain an accurate blood pressure (BP) measurement, especially in the prehospital environment. It is not known fully how various BP measurement techniques differ from one another. STUDY OBJECTIVE: The study hypothesized that there are differences in the accuracy of various non-invasive blood pressure (NIBP) measurement strategies as compared to the gold standard of intra-arterial (IA) measurement. METHODS: The study enrolled adult intensive care unit (ICU) patients with radial IA catheters placed to measure radial intra-arterial blood pressure (RIBP) as a part of their standard care at a large, urban, tertiary-care Level I trauma center. Systolic blood pressure (SBP) was taken by three different NIBP techniques (oscillometric, auscultated, and palpated) and compared to RIBP measurements. Data were analyzed using the paired t-test with dependent samples to detect differences between RIBP measurements and each NIBP method. The primary outcome was the difference in RIBP and NIBP measurement. There was also a predetermined subgroup analysis based on gender, body mass index (BMI), primary diagnosis requiring IA line placement, and current vasoactive medication use. RESULTS: Forty-four patients were enrolled to detect a predetermined clinically significant difference of 5mmHg in SBP. The patient population was 63.6% male and 36.4% female with an average age of 58.4 years old. The most common primary diagnoses were septic shock (47.7%), stroke (13.6%), and increased intracranial pressure (ICP; 13.6%). Most patients were receiving some form of sedation (63.4%), while 50.0% were receiving vasopressor medication and 31.8% were receiving anti-hypertensive medication. When compared to RIBP values, only the palpated SBP values had a clinically significant difference (9.88mmHg less than RIBP; P < .001). When compared to RIBP, the oscillometric and auscultated SBP readings showed statistically but not clinically significant lower values. The palpated method also showed a clinically significant lower SBP reading than the oscillometric method (5.48mmHg; P < .001) and the auscultated method (5.06mmHg; P < .001). There was no significant difference between the oscillometric and auscultated methods (0.42mmHg; P = .73). CONCLUSION: Overall, NIBPs significantly under-estimated RIBP measurements. Palpated BP measurements were consistently lower than RIBP, which was statistically and clinically significant. These results raise concern about the accuracy of palpated BP and its pervasive use in prehospital care. The data also suggested that auscultated and oscillometric BP may provide similar measurements.