Inconsistent findings in the studies have been observed concerning the higher dose of statins use in the acute phase of ischemic stroke and transient ischemic attack (TIA). Therefore, we performed a systematic review to assess this issue. A computerized literature search in PubMed, Cochrane Library databases, and EMBASE for randomized controlled trials (RCTs) was conducted. The efficacy outcome indicators were National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and recurrence of stroke; the safety outcome indicators were intracranial hemorrhage events, cardiovascular and cerebrovascular events, and all-cause death. Pre-specified subgroup analyses were carried out. A total of seven RCTs with 1089 patients were included. Six studies reported the results of the NHISS score. A great reduction was found in NIHSS score in the statins group, and the difference is statistically significant [mean difference (MD) -1.15, 95% confidence interval (CI) -1.64 to -0.66, P < 0.00001]. However, no significant differences in the effect on recurrence of stroke [odds ratio (OR) 1.05, 95% CI 0.65-1.69, P = 0.85] (available in 3 studies), infarct volume [std. mean difference (SMD) 0.04, 95% CI -0.55 to 0.63, P = 0.89] (available in 2 studies), intracerebral hemorrhage events (OR 3.25, 95% CI 0.34-31.52, P = 0.31) (available in 2 studies), cardiovascular and cerebrovascular events (OR 0.70, 95% CI 0.35-1.43, P = 0.33) (available in 2 studies), and all-cause death (OR 1.18, 95% CI 0.60-2.35, P = 0.63) (available in 2 studies) were found. High-dose statin therapy in the acute phase of ischemic stroke and TIA significantly reduce the NIHSS score and improve short-term functional outcome without increasing related adverse events.