Statin withdrawal is associated with deleterious outcome on stroke patients. Whether risk changes over time, depends on concomitant treatment of intravenous thrombolysis, or both remains to be clarified. We assessed the influence of statin withdrawal within 3 weeks while initiated in acute phase (72 hours) among patients receiving intravenous thrombolysis.This was a monocentered retrospective observational study enrolling intravenous thrombolytic stroke patients from June 2009 to May 2014. Consecutive patients were distinguished into 3 groups according to the initiation and withdrawal of statin: the reference group (not received statin in 72 hours after stroke onset); the continued group (initiated statin therapy in 72 hours and continued for at least 3 weeks); the withdrawal group (initiated statin in 72 hours and discontinued within 3 weeks). All reasons for cessation were recorded. The effects of statin withdrawal on short-, mid-, and long-term outcomes were evaluated as neurologic improvement (NIH Stroke Scale [NIHSS] score improvement ≥4 from baseline or later NIHSS = 0), death or poor outcome (modified Rankin Scale [mRS] ≥4), and favorable outcome (mRS ≤2). We further evaluate statin withdrawal effects in cardioembolic stroke patients for these outcomes.Among 443 IVT patients enrolled, 367 were included in the final study population. There were 88, 188, and 91 patients in the reference, continued, and withdrawal groups, respectively. Multivariable logistic regression showed that statin withdrawal compared with the reference was related to a lower possibility of long-term favorable outcome (OR = 0.45, 95% CI [0.22, 0.90], P = 0.024). Compared with the continued group, the adjusted OR of statin withdrawal was 0.40 (95% CI [0.22, 0.72], P = 0.002) and 2.52 (95% CI [1.34, 4.75], P = 0.004) for long-term favorable and poor/death outcomes, respectively. Also, results were similar for cardioembolic stroke patients (OR = 0.35, 95% CI [0.14, 0.89], P = 0.027 of favorable outcome and OR = 3.62, 95% CI [1.37, 9.62], P = 0.010 of poor/death outcome).In a real-world setting, for stroke patients receiving intravenous thrombolysis, statin withdrawal within 3 weeks initiating in 72 hours may have a harmful effect on the long-term neurologic outcome, even in cardioembolic stroke patients.