We enrolled 33 patients (16 men/17 women, age range 23-82 years). Three patients were treated at 1 mg/kg, 10 at 3 mg/kg, 12 at 6 mg/kg, and 8 at 8 mg/kg. Thirty of the 33 patients (90.9%) completed at least 11 of 12 doses. Two patients at the 6-mg/kg dose level experienced transient mild elevations in transaminases without clinical sequelae. After an initial dose reduction, the dose was re-escalated to 8 mg/kg, and no further patients reached safety outcomes. No clinical liver disease, myopathy, or creatine phosphokinase elevations occurred. The final model-based toxicity at 8 mg/kg was 13%; no patient was treated at 10 mg/kg. In conclusion, Lovastatin at doses above those currently approved by the Food and Drug Administration is feasible for 3 days after an acute ischemic stroke and the maximum tolerated dose is estimated to be 8 mg/kg/day. Further randomized studies are warranted to confirm its safety and to demonstrate its efficacy in improving functional outcomes after stroke.