Anticoagulation treatment during extracorporeal membrane oxygenation (ECMO) treatment is unavoidable. However, discontinuation of heparin infusion is necessary when challenges associated with the use of heparin, such as bleeding and thrombocytopenia, are encountered. The medical records of 94 adult (age ≥ 18 years) patients treated with ECMO from January 2011 to March 2015, at Chung-Ang University Hospital, Seoul, Korea, were reviewed. Among the 94 patients, 55 patients underwent ECMO treatment for three or more days. In 52.7% of these patients (n = 29, group A), heparin was stopped for three or more days because of thrombocytopenic events (< 50,000 cells/mm), higher than target range (> 230 seconds) activated clotting time (ACT), bleeding complications, or the need for other surgical procedures. In 43.6% of patients (n = 24, group B), heparin was continuously infused during the entire ECMO process. The mean length of ECMO support after the initiation of heparin discontinuation in patients in group A was 10.2 ± 14.7 days. There were no intracardiac, intravascular, or intracircuit thrombotic complications in group A. There was no difference in the ECMO weaning success rate between the two groups (41.4% in group A vs. 54.2% in group B, p = 0.353). Heparin discontinuation can be considered in a select group of patients with coagulation abnormalities or bleeding.