Standard treatment for eligible patients presenting with acute ischemic stroke (AIS) is thrombolysis with tissue plasminogen activators alteplase or tenecteplase. Current guidelines recommend monitoring patients in an intensive care unit (ICU) for 24h after thrombolytic therapy. However, recent studies have questioned the need for prolonged ICU monitoring. This retrospective cohort study aims to identify potential candidates for early transition to a lower level of care by assessing risk factors for neurological deterioration, symptomatic intracranial hemorrhage (sICH), or need for ICU intervention within 24h post-thrombolysis. This retrospective cohort study included adult patients 18years and older with AIS who received thrombolysis. Patients were excluded if they were transferred to another facility, if they were transitioned to comfort care or hospice care within 24h, or if they lacked imaging and National Institutes of Health Stroke Scale (NIHSS) score data. The primary end point was incidence of sICH between 0-12 and 12-24h. Secondary end points included the need for ICU intervention and rates of neurological deterioration. The analysis included 204 patients who received the full dose of alteplase. Among them, ten patients (4.9%) developed sICH, with the majority (n = 7) occurring within 12h post-thrombolysis. Sixty-two patients required ICU interventions within 12h compared with four patients after 12h. Twenty-four patients had neurological deterioration within 12h, and seven patients had neurological deterioration after 12h. Multivariable analysis identified mechanical thrombectomy and increased blood pressure at presentation as predictors of ICU need beyond 12h post-thrombolysis. Our study demonstrates that sICH, neurological deterioration, and need for ICU intervention rarely occur beyond 12h after thrombolytic administration. Patients presenting with blood pressures < 140/90mm Hg, NIHSS scores < 10, and not undergoing mechanical thrombectomy may be best candidates for early de-escalation. Larger prospective studies are needed to more fully evaluate the safety, feasibility, and financial impact of early transition out of the ICU.