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Objectives Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt‐PA. Here, we performed a systematic review and meta‐analysis to assess the safety and efficacy of thrombolysis in these patients. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched in July 2018. All available RCTs and retrospective comparative studies that compared thrombolysis with nonthrombolysis' for acute minor stroke (NIHSS ≤ 5) with quantitative outcomes were included. Results Ten studies, including a total of 4,333 patients, were identified. The risk of intracranial hemorrhage (ICH) was higher in the rt‐PA group as compared with that in the non‐rt‐PA group (3.8% vs. 0.6%; p = .0001). However, there is no significant difference in the rate of mortality between the two groups (p = .96). The pooled rate of a good outcome in 90 days was 67.8% in those with rt‐PA and 63.3% in those without rt‐PA (p = .07). Heterogeneity was 43% between the studies (p = .08). After adjusting for the heterogeneity, thrombolysis was associated with good outcome (68.3% vs. 63.0%, OR 1.47; 95% CI 1.14–1.89; p = .003). In post hoc analyses, including only RCTs, the pooled rate of good outcome had no significant differences between the two groups (86.6% vs. 85.7%, 95% CI 0.44–3.17, p = .74; 87.4% vs. 91.9%, 95% CI 0.35–1.41, p = .32; before and after adjusting separately). Conclusions Although thrombolysis might increase the risk of ICH based on existing studies, patients with acute minor ischemic stroke could still benefit from thrombolysis at 3 months from the onset., Although there were some studies assessed the efficacy of thrombolysis for minor stroke, lack of a systematic review. We performed a meta‐analysis study showed that acute minor ischemic stroke patients might benefit from thrombolysis at 3 months, although thrombolysis could increase the risk of ICH based on existing studies.