Background: Critically ill patients requiring extracorporeal membrane oxygenation (ECMO) have several risk factors to suffer from abdominal compartment syndrome (ACS). Little is known about this subgroup. The aim of this study was to investigate the prevalence and associated factors for ACS in patients requiring ECMO to assess the effect of decompressive laparotomy (DL) and the impact on mortality. Methods: This retrospective observational study analyzed adult patients requiring ECMO in four intensive care units at the University Medical Center Regensburg between 01/2010 and 06/2020. Patients with clinically suspected ACS were screened by measuring intra-abdominal pressure (IAP) with the trans-bladder technique. ACS was defined as IAP > 20 mmHg and survival was defined as successful discharge from hospital. Results: The prevalence of ACS in non-ECMO ICU patients was 0.8% (291/36,795) and 2.9% (47/1643) in ECMO patients. In the subgroup of resuscitated ECMO patients, ACS was present in 4.2% (32/766). Procalcitonin was associated with ACS. ECMO patients with ACS receiving DL were significantly more ill compared to those without DL (SOFA score at ICU admission 18 [15; 20], vs. 16 [13; 17], p = 0.048). DL decreased IAP and significantly improved ventilation; vasopressor and lactate stabilized within 24 hours. Survival was comparable between the DL and the non-DL groups (11% [1/9] vs. 14% [1/7], p = 1.000). Conclusions: ECMO patients are at high risk of developing ACS, even more so for resuscitated patients. This and high procalcitonin may be taken into consideration when screening for ACS. Decompressive laparotomy did improve respiratory compliance and stabilized hemodynamic parameters with low rates of complication. Even though patients that received DL were significantly more ill, the mortality rates were not higher.