BACKGROUND AND PURPOSE: Since the introduction of recombinant tissue plasminogen activator (rtPA) into clinical practice in the mid 1990s, no adjunctive treatment has further improved clinical outcomes in patients with ischemic stroke. The safety, feasibility, and efficacy of combining intravenous (IV) rtPA with endovascular interventions has been described; however, no direct comparative study has yet established whether endovascular interventions after IV rtPA are superior to IV rtPA alone. A retrospective case-control study was designed to address this issue. MATERIALS AND METHODS: Between 2003 and 2006, 33 consecutive patients with acute ischemic stroke and National Institutes of Health Stroke Scale (NIHSS) scores ≥10 were treated with IV rtPA in combination with endovascular interventions (IV plus intervention) at a tertiary care facility. Outcomes were compared with a control cohort of 30 consecutive patients treated with IV rtPA (IV only) at a comparable facility where endovascular interventions were not available. RESULTS: Baseline parameters were similar between the 2 groups. We found that the IV-plus-intervention group experienced significantly lower mortality at 90 days (12.1% versus 40.0%, P = .019) with a significantly greater improvement in NIHSS scores by the time of discharge or follow-up (P = .025). In the IV-plus-intervention group, patients with admission NIHSS scores between 10 and 15 and patients ≤80 years of age showed the greatest improvement, with a significant change of the NIHSS scores from admission (P = .00015 and P = .013, respectively). CONCLUSIONS: In this small case-control study of patients with acute ischemic stroke and admission NIHSS scores ≥10, there was a suggestion of incremental clinical benefit among patients receiving endovascular interventions following standard administration of IV rtPA.