To determine whether elevated intra-abdominal pressure (IAP) is associated with a higher rate of enteral nutrition-related gastrointestinal (GI) complications; to assess the value of IAP as a predictor of enteral nutrition (EN) intolerance. Intensive Care Unit (ICU) patients on mechanical ventilation requiring at least 5 days of EN were recruited for a prospective, observational, non-interventional, multicenter study. EN was performed and GI complications were managed with an established protocol. IAP was determined via a urinary catheter. Patients who developed any GI complications were considered as presenting EN intolerance. Variables related to EN, IAP and GI complications were monitored daily. Statistical analysis compared patients without GI complications (group A) vs. GI complications (group B). 247 patients were recruited from 28 participating ICUs (group A: 119, group B: 128). No differences between groups were recorded. Patients in group B (p < 0.001) spent more days on EN (8.1 ± 8.4 vs. 18.1 ± 13.7), on mechanical ventilation (8.0 ± 7.7 vs. 19.3 ± 14.9) and in the ICU (12.3 ± 11.4 vs. 24.8 ± 17.5). IAP prior to the GI complication was (14.3 ± 3.1 vs. 15.8 ± 4.8) (p < 0.003). The best IAP value identified for EN intolerance was 14 mmHg but it had low sensitivity and specificity. Although a higher IAP was associated with EN intolerance, IAP alone did not emerge as a good predictor of EN intolerance in critically ill patients.