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Background: Several major trials assessing ischemic stroke therapy with endovascular revascularization have shown better clinical and functional outcomes. A systematic review and pooled analyses of six recent multi-centered prospective randomized control trials (MPRCT) was performed to compare intravenous tissue plasminogen activator (IV tPA) and endovascular therapy (intervention) with IV tPA alone (control). We sought to evaluate the role of time of onset to groin puncture in determining outcome after endovascular therapy.Methods: We reviewed the results of the six most recent MPRCTs: MR CLEAN, ESCAPE, IA EXTEND, SWIFT PRIME, REVASCAT and THERAPY. To be included, trials pre-specified primary clinical outcomes of AIS patients in intervention and control arms. We categorized outcome at 90 days as "good" with modified Rankin Scale (mRS) of 0-2, "moderate" with mRS of 3-4, and "bad" with mRS of 5-6. We looked at recorded symptom onset to groin puncture (STG) times, compared them with the percentage of patients in the good, moderate and bad category and found correlations between the times from onset to groin puncture and the category of outcome. SPSS Version 22 was used for all statistical analysis.Results: A total of 1,386 patients were included. Good outcomes at 90-days were seen in 46% patients in intervention (p<.00001) and 27% of patients in control (p<.00002). mTICI 2b/3 was achieved in 70.2 % patients in intervention arm. Patients with good outcome (mRS 0-2), had a mean STG of 176 minutes (p= .0001), those with moderate outcome (mRS 3-4) had a mean STG of 195 minutes (p=.0001), and those with bad outcome (mRS 5-6), had a mean STG of 208 minutes (p= .0001). A longer STG time correlated with bad outcome (r= .815; p<.05).Conclusion: Endovascular therapy combined with IV tPA was superior to IV tPA alone. However, time is still of the essence and the longer delays to groin puncture were associated with more death and disability. More efforts should aim toward reducing the time of stroke onset to groin puncture time. Data on the reasons for delays should be reviewed to better understand where reductions in time are most applicable.