Background: 24h CT is routinely acquired post-thrombolysis. Parenchymal hematoma and brain edema are feared complications. Predicting complications that change management would help reduce unnecessary imaging. Objective: To evaluate the utility of 24h per-protocol CT scan for stroke patients after thrombolysis. Methods: A prospectively collected cohort of consecutive patients presenting with acute ischemic stroke to our hospital from 2013- 2021 who were treated with IV tPA without undergoing endovascular therapy was entered into our IRB-approved stroke registry. Neuroimaging performed within 48h after admission was reviewed. Patients’ demographics, past medical history, admission National Institute of Health Stroke Scale (NIHSS) score, and medical variables were obtained. The primary outcome was significant radiologically findings (parenchymal hematoma or midline shift/herniation) leading to change in management (additional monitoring, emergent procedure, administration of mannitol or alteration in blood pressure goal). Results: From 2013 to 2021, 875 patients (mean age 69) who had IV tPA without undergoing endovascular therapy were identified, of which 472 (47.1%) were female. Median (IQR) NIHSS score was 9 (4-16) on admission. Imaging findings: 339 (38.7%) had expected evolving infarctions; 106(13.3%) developed any type of hemorrhagic transformation, including 66 (7.5%) who had hemorrhagic infarction and 50 (5.7%) parenchymal hematomas; 142(16.2%) developed any kind of mass effect, including 63 (7.2%) who had mild mass effect and 79 (9.0%) midline shift/herniation. There were 124 patients (12.1%) had significant findings (including parenchymal hematoma and midline shift/brain herniation) leading to change in the management. Patients who had significant findings had higher NIHSS score 16 (8-21) than those without 8 (4-15) (p<0.001). NIHSS was the only significant outcome predictor both in univariate and the multivariable analysis. Conclusions and interpretations: Our study showed that patients with high NIHSS score were more likely to have significant findings. 24-hour follow-up CT scan should be based on the risk of developing significant complications.