Oxygenator thrombosis is a major complication during extracorporeal membrane oxygenation (ECMO), but systemic anticoagulation may be contraindicated by active hemorrhage, recent surgery, intracranial injury, or severe coagulopathy. Circuit-directed nitric oxide (NO) delivered into the oxygenator sweep gas may provide localized antiplatelet activity at the blood–circuit interface without intentionally producing systemic anticoagulation. We conducted a single-center retrospective case series of adult extracorporeal membrane oxygenation (ECMO) patients treated between January 1, 2025, and May 31, 2026, who received circuit-directed NO while systemic anticoagulation and antiplatelet therapy were withheld due to clinically significant bleeding risk. Nitric oxide was delivered at 20 ppm via a NOxBOXi system connected to the oxygenator sweep-gas pathway. Ten patients received circuit-directed NO: three venovenous, six venoarterial, and one venopulmonary arterial, for durations of 2–72 days. No patient required oxygenator exchange for thrombosis, gas-exchange failure, progressive trans-oxygenator pressure-gradient elevation, or hemolysis. The trans-oxygenator pressure gradient remained below 50 mm Hg in all patients. Maximum methemoglobin ranged from 1.0% to 3.4%, and no patient required NO discontinuation. Nine of 10 patients survived to decannulation. In this small uncontrolled series, circuit-directed NO was feasible and not associated with NO-attributable safety events or oxygenator exchange; efficacy cannot be inferred.