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Background: Mild stroke (National Institutes of Health Stroke Scale [NIHSS] score of 0-4) accounts approximately for one third of patients that present in three hours after onset of stroke. And about 30% of patients, who are considered having mild stroke, suffer from clearly disabling deficits at 90 days. Although prior major trials of alteplase included patients with low NIHSS scores, the safety and efficacy of alteplase in such patients are still controversial.Purposes: To evaluate the efficacy and safety of alteplase in patients with NIHSS scores of 0 to 4 in the first 4.5 hours after onset.Methods and main outcomes: Prospective case series study in 50 mild stroke patients who were admitted in Peopleu2019s hospital 115 and University Medical Center of Ho Chi Minh city in 4.5 hours from the symptoms onset between November 2017 and July 2018. Favorable outcome (Modified Rankin Score [mRS] of 0-1) at 90 days, symptomatic intracerebral hemorrhage, mortalities of all causes at 90 days were evaluated to determine the association with alteplase treatment.Results: Alteplase was administered to 27 of 50 patients (54 %). 73 % of patients in the alteplase group vs 63.2 % in the untreated group achieved a favorable outcome at 90 days, but not significantly different (p= 0.48; CI 95 %). The incidence of symptomatic intracerebral hemorrhage according to SITS-MOSTu2019s criteria and the mortality rate was not significantly different between the two groups- (0% in both groups); (3.7 % vs 4.3 %; p= 1; CI 95%).Multivariable logistic regression analysis of favorable outcome revealed that the significant independent factors were age of 70 or older (OR, 0.125; 95 % CI, 0.026 - 0.591); History of diabetes (OR, 0.066; 95% CI, 0.006 - 0.795).Conclusions: Alteplase treatment can be safe and has effective trend in patients with mild stroke.