Background Intra-abdominal hypertension affects multiple organ systems. Current measurement standard requires supine positioning, which jeopardizes patient safety by increasing the risk for ventilator-associated pneumonia. This study evaluated the relationship between intra-abdominal pressure (IAP) and head-of-bed (HOB) positioning in critically ill intubated patients. Methods IAP measurements were performed using intravesical catheters with manometry. IAP was measured in a range of patient HOB increases from 0° to 45°. Multivariable generalized estimating equation modeling was performed to describe the relationship between IAP and HOB positioning. Results Three hundred (300) observations were performed on 37 patients. In multivariable modeling, HOB increase was significantly associated with IAP. Body mass index, positive end-expiratory pressure, temperature, and diagnostic category were significant in this model, whereas age and Riker sedation score were not. Conclusions There is a significant, positive association between IAP and HOB positioning in critically ill patients. Clinically relevant changes in IAP occur at HOB increases >20°.