In a post-hoc analysis of the single-center randomized Prague-OHCA trial, Smalcova et al. evaluated whether early bedside signs of non-occlusive mesenteric ischemia (NOMI), specifically watery watery diarrhea and abdominal distension within 12 hours of admission, were associated with 180-day neurological outcomes in adults with refractory out-of-hospital cardiac arrest (OHCA) treated with either an ECPR-based invasive strategy or conventional CPR. The parent trial enrolled 256 adults who witnessed OHCA of presumed cardiac origin and no prehospital return of spontaneous circulation (ROSC), randomizing 124 to the invasive (ECPR-based) strategy and 132 to standard care (median age 58 y, ~17% women). This secondary analysis included all patients who survived one hour after hospital admission. The primary endpoint was unfavorable neurological outcome at day 180, defined as Cerebral Performance Category (CPC) 3-5. Of the 180 participants, 61 developed possible NOMI: 46 of 89 (51.7%) in the ECPR group and 15 of 91 (16.5%) in the standard CPR arm. Unfavorable neurological outcomes occurred in 41 of 46 (89%) ECPR patients with possible NOMI and 9 of 15(60%) CPR patients with possible NOMI. Possible NOMI correlated with longer arrest duration and higher neuron-specific enolase at 48-72 hours. In multivariable analysis, possible NOMI was independently associated with adverse neurological outcomes in multivariable modeling–particularly among ECPR patients (OR 8.06, 95% CI 1.74-37.4). Early clinical signs of NOMI were substantially more prevalent among patients managed with an ECPR-based strategy and were independently associated with unfavorable 180-day neurological outcomes. These findings suggest that intestinal ischemia-reperfusion injury may be a clinically relevant marker, or even a potential mediator of subsequent neurological injury in refractory OHCA, particularly during ECPR support, and warrant prospective validation with standardized diagnostic criteria and mechanistic endpoints.