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Blood pressure measurements frequently guide management in critical care. Direct readings, commonly from a major artery, are considered to be the gold standard. Because arterial cannulation is associated with risks, alternative noninvasive blood pressure (NIBP) measurements are routinely used. However, the accuracy of NIBP determinations in overweight patients in the outpatient setting is variable, and little is known about critically ill patients. This prospective, observational study was performed to compare direct intra-arterial blood pressure (IABP) with NIBP measurements obtained using auscultatory and oscillometric methods in overweight patients admitted to our medical intensive care unit. Adult critically ill patients with a body mass index (BMI) of 25 kg/m2 or greater and a functional arterial line (assessed using the rapid flush test) were enrolled in the study. IABP measurements were compared with those obtained noninvasively. A calibrated aneroid manometer (auscultatory technique) with arm cuffs compatible with arm sizes and a NIBP monitor (oscillometric technique) were used for NIBP measurements. Agreement between methods was assessed using Bland-Altman analysis. Fifty-four patients (23 males) with a mean (± standard error) age of 57 ± 3 years were studied. The mean BMI was 34.0 ± 1.4 kg/m2. Mean arm circumference was 32 ± 0.6 cm. IABP readings were obtained from the radial artery in all patients. Only eight patients were receiving vasoactive medications. Mean overall biases for the auscultatory and oscillometric techniques were 4.1 ± 1.9 and -8.0 ± 1.7 mmHg, respectively (P < 0.0001), with wide limits of agreement. The overestimation of blood pressure using the auscultatory technique was more important in patients with a BMI of 30 kg/m2 or greater. In hypertensive patients both NIBP methods underestimated blood pressure as determined using direct IABP measurement. Oscillometric blood pressure measurements underestimated IABP readings regardless of patient BMI. Auscultatory measurements were also inaccurate, tending to underestimate systolic blood pressure and overestimate mean arterial and diastolic blood pressure. NIBP can be inaccurate among overweight critically ill patients and lead to erroneous interpretations of blood pressure.