Hybrid extracorporeal membrane oxygenation (ECMO), containing additional ECMO cannulations in addition to conventional ECMO, is increasingly used for the treatment of serious cardiopulmonary conditions. Patients initiating non-hybrid ECMO may transition to hybrid ECMO as their condition worsens. This study compared mortality rates between patients initially on hybrid ECMO and those who transitioned from non-hybrid to hybrid ECMO. We also examined complications related to hybrid ECMO, comparing them with those of non-hybrid ECMO. Data from PubMed, Embase, and Cochrane databases were analyzed using Peto odds ratios and 95% confidential intervals (CIs), with an additional safety comparison to the Extracorporeal Life Support Organization registry to overcome the small number of selected studies. A meta-analysis was performed using review manager. The mortality rate did not differ significantly between whether the hybrid ECMO was used initially or transitioned from non-hybrid ECMO during treatment. Renal-related complications were the most frequent in both hybrid and non-hybrid ECMO cases, with overall higher complication rates in hybrid ECMO. The study concludes that transitioning to hybrid ECMO during treatment does not increase mortality compared to starting with hybrid ECMO, but potential complications, especially with commodity conditions, should be considered. This study provides valuable guidance for clinicians choosing ECMO modalities in clinical practice.