Objective To explore the impact of obesity on poor prognosis of recombinant tissue plasminogen activator （rt-PA） intravenous thrombolysis in patients with first-episode acute ischemic stroke. Methods From December 2017 to December 2023， 297 patients with first-episode stroke who underwent rt-PA intravenous thrombolysis in the Department of Neurology of Suzhou Ninth Hospital affiliated to Soochow University were selected as participants. According to the 90 days Modified Rankin Scale （mRS） score， patients were divided into a poor prognosis group （mRS score of 3 to 6） and a good prognosis group （mRS score of 0 to 2）. Multivariate Logistic regression was used to analyze the risk factors for poor 90-day prognosis in patients with acute ischemic stroke undergoing intravenous thrombolysis. Results Among 297 patients with first-episode acute ischemic stroke， 212 had good prognosis and 85 had poor prognosis， with a poor prognosis rate of 28.62%. In the poor prognosis group， obese patients （BMI ≥ 28.0 kg/m2 ） accounted for 27.06% （23/85）， smoking patients accounted for 31.76% （27/85）， and the National Institute of Health Stroke Scale （NIHSS） score before thrombolysis was 13.00 （9.50， 18.00）， which were higher than the good prognosis group's 16.98% （36/212）， 20.28% （43/212）， and 7.00 （5.00， 11.00）， respectively， and the differences were statistically significant （χ2 /Z=3.871， 4.440， -8.013； P ＜ 0.05）. Multivariate Logistic regression analysis showed that obesity （OR=2.918， 95%CI=1.364-6.242）， smoking （OR=3.648， 95%CI=1.678-7.931）， and high pre-thrombolysis NIHSS score （OR=1.269， 95%CI=1.184-1.361） were risk factors for poor prognosis in patients with acute ischemic stroke undergoing intravenous thrombolysis， with statistically significant differences （P＜ 0.05）. Conclusions Obesity is a risk factor for poor prognosis after 90 days of intravenous thrombolysis in patients with first-episode ischemic stroke.