This systematic review and meta-analysis compared the efficacy of reduced-intensity or no-heparin versus standard heparin anticoagulation in patients on extracorporeal membrane oxygenation (ECMO). It included 5 patient analyses, with four studies focusing exclusively on veno-venous ECMO (V-V ECMO) in acute respiratory distress syndrome or respiratory failure, two on veno-arterial ECMO (V-A ECMO) and five on patients with both types. Most of the 8 studies were of high quality with a Newcastle-Ottawa score ≥ 6. The overall incidence of bleeding complications was 34% (95% CI: 0.35–0.67) with heterogeneity I² = 43%. The incidence of thrombotic events was 14.6% (95% CI: 0.65–1.54; I² = 49%), in-hospital mortality was 49% (95% CI: 0.67–1.21; I² = 41%), and the RBC transfusion rate was 41.2% (95% CI: 0.08–1.02; I² = 76%). These strategies may be associated with a reduction in complications without a significant increase in thrombotic events. The study is registered under PROSPERO CRD42025633878.