Patients who undergo extracorporeal cardiopulmonary resuscitation (ECPR) are at risk of left ventricular distention and complications. There is emerging evidence that concurrent mechanical left ventricular (LV) unloading (e.g. an intra-aortic balloon pump, or microaxial left ventricular assist device) may improve survival. Despite this, there are no large, well-conducted studies investigating the impact of LV unloading on outcomes in ECPR.We queried the Extracorporeal Life Support Organisation (ELSO) registry between 2020 and 2023, and used an emulated target trial framework to investigate the association between concurrent mechanical left ventricular unloading and outcomes in patients receiving ECPR. We imputed missing data using multiple imputation with chained equations, and identified potential confounders implicated in the causal pathway between ECPR and survival time up to 90 days (primary outcome). We used propensity score-matching to adjust for potential confounders, and analysed the primary outcome using a Cox proportional hazards model. We then emulated further target trials based on the inclusion criteria of prior ECPR RCTs to assess whether concurrent unloading was associated with better outcomes based on these criteria. Secondary outcomes included complications from ECPR as classified by ELSO, and survival with favourable functional outcome defined as a Cerebral Performance Category (CPC) 1-2.Of the 3,215 patients included in our analysis, we matched 621 pairs of patients who did and did not receive LV unloading. There were no significant differences in survival time between both groups (HR 0.92, 95%-CI 0.79-1.08), nor survival with favourable functional outcomes (OR 1.15, 95%-CI 0.67-1.99). This was concordant across several sensitivity analyses. Of note, LV unloading was associated with a higher rate of renal (OR 1.55, 95%-CI 1.16-2.07) and cardiovascular (OR 1.60, 95%-CI 1.14-2.26) complications. LV unloading was also associated with central nervous system bleeding (OR 1.75, 95%-CI 1.03-2.96), arrhythmias (OR 1.56, 95%-CI 1.04-2.36), and haemolysis (OR 1.85, 95%-CI 1.10-3.09).Left ventricular unloading was not associated with improved survival in the context of ECPR and may increase complication rates. Randomised data are required to confirm these findings.