Background Intravenous thrombolysis (IVT) with alteplase is the first-line therapy for acute ischemic anterior and posterior circulation strokes (ACS and PCS). Knowledge about safety and efficacy of IVT in posterior circulation stroke is deficient as most of the Egyptian studies either assessed IVT outcome in comparison to conservative therapy or its outcome in anterior circulation stroke only. Therefore, our aim was to compare the relative frequency and outcome after intravenous thrombolysis in anterior versus posterior circulation stroke patients presenting to stroke centers of Ain Shams University hospitals (ASUH). Results A total of 238 anterior circulation stroke and 61 posterior circulation strokes were enrolled, onset-to-door and door-to-needle time were statistically insignificant. NIHSS showed comparable difference at all time points despite higher scores along anterior circulation stroke; 90-day modified Rankin Scale (mRS) showed significant improvement in both groups from mRS >2 to ≤2 with a better percentage along posterior circulation stroke patients. There was insignificant difference for either incidence of death or intracranial hemorrhage (ICH) between the two groups. Conclusion IVT significantly reduced NIHSS for both anterior and posterior circulation stroke along different studied time points. Meanwhile, a higher percentage of patients with posterior circulation stroke had a better mRS outcome at 90 days.