The risk of ischemic stroke is an emergent concern in the Kingdom of Saudi Arabia. Recent studies indicate that cardiovascular conditions account for 33% of deaths each year in Saudi Arabia. The benefits of t-PA for acute ischemic stroke within the first 4-5 hours after the onset of stroke are established in the literature. However, a considerably small patient population receives this type of treatment. The underutilization of recombinant tissue-type plasminogen activator (t-PA) arises due to several reasons, including the lack of information and awareness about recognition and response to stroke signals, risk of symptomatic intracerebral hemorrhage, and complexities involved in stroke care. Using a cross-sectional study design consisting of 127 emergency Saudi physicians, this study assessed emergency physicians' knowledge about recombinant tissue plasminogen activator for acute ischemic stroke. Emergency physicians are less likely to use RT-PA in the treatment of acute ischemic stroke due to hemorrhage risk and lack of benefit in neurological outcome. Knowledge in emergency physicians was found to be approximately the same for both experienced and non-experienced physicians.