Venovenous extracorporeal membrane oxygenation (ECMO) is recommended in adult patients with refractory acute respiratory failure (ARF), but there is limited evidence for its use in patients with less severe hypoxemia. Prior research has suggested a lower PaO₂/FiO₂ at cannulation is associated with higher short-term mortality, but it is unclear whether this is due to less severe illness or a potential benefit of earlier ECMO support. In this exploratory cardinality-matched observational cohort study, we matched 668 patients who received venovenous ECMO as part of a national severe respiratory failure service into cohorts of “less severe” and “very severe” hypoxemia based on the median PaO₂/FiO₂ at ECMO institution of 68 mmHg. Before matching, ICU mortality was 19% in the ‘less severe’ hypoxemia group and 28% in the “very severe” hypoxemia group (RR for mortality = 0.69, 95% CI 0.54–0.88). After matching on key prognostic variables including underlying diagnosis, this difference remained statistically present but smaller: (23% vs. 30%, RR = 0.76, 95% CI 0.59–0.99). This may suggest the observed survival benefit of venovenous ECMO is not solely due to reduced disease severity. Further research is warranted to examine the potential role of ECMO in ARF patients with less severe hypoxemia.