The use of mechanical circulatory support (MCS) in cardiogenic shock (CS) is increasing. We conducted a systematic review and meta-analysis to compare the outcomes of Impella use with extracorporeal membranous oxygenation (ECMO) support in patients with CS. We searched the Medline, EMBASE, Cochrane, and Clinicaltrials.gov databases for observational studies comparing Impella to ECMO in patients with CS. Risk ratios (RRs) for categorical variables and standardized mean differences (SMDs) for continuous variables were calculated with 95% confidence intervals (CIs) using a random-effects model. Twelve retrospective studies and one prospective study (Impella n=6652, ECMO n=1232) were identified. Impella use was associated with lower incidence of in-hospital mortality (RR 0.88 [95% CI 0.80-0.94], P=0.0004), stroke (RR 0.30 [0.21-0.42], P<0.00001), access-site bleeding (RR 0.50 [0.37-0.69], P<0.0001), major bleeding (RR 0.56 [0.39-0.80], P=0.002), and limb ischemia (RR 0.42 [0.27-0.65], P=0.0001). Baseline lactate levels were significantly lower in the Impella group (SMD -0.52 [-0.73- -0.31], P<0.00001). There was no significant difference in mortality at 6-12 months, MCS duration, need for MCS escalation, bridge-to-LVAD or heart transplant, and renal replacement therapy use between Impella and ECMO groups. In patients with CS, Impella device use was associated with lower in-hospital mortality, stroke, and device-related complications than ECMO. However, patients in the ECMO group had higher baseline lactate levels.