The influence of baseline stroke severity on outcome makes comparisons between nonrandomized studies of intravenous and intra-arterial (IA) therapy problematic. Using pooled data from the placebo arms of randomized trials in acute ischemic stroke, we derived predictive functions for outcome. We then compared the outcomes from published trials to these functions. Net benefit was calculated by comparison of the individual study with the predicted outcome based on the therapeutic time window. Similar net benefit for IA therapy and intravenous therapy was found at 3 hours and 6 hours; a slight advantage for IA therapy was mitigated by an increase in mortality at 6 hours and by publication bias. No net benefit for IA therapy was shown in the time window greater than 6 hours. Conclusive evidence for the superiority of either therapy awaits prospective randomized trials.