Background and Objective. Thrombolytics and anticoagulants are conventional drugs for ischemic stroke (IS) treatment, whereas some patients have unfavorable responses to these drugs. The disease presents a relatively high recurrence rate. This investigation attempted to unveil the long-term effect of left atrial appendage occlusion (LAAO) in treating patients with previous IS on the disease recurrence. Methods. A total of 120 patients with IS admitted to Tangdu Hospital from July 2016 to September 2017 were grouped into the control group (
n
=
60
) and the observation group (
n
=
60
). Patients in the control group were only treated with thrombolytics and anticoagulants while those in the observation group were treated with both drugs and LAAO. Transesophageal echocardiography (TEE) was performed to observe the occlusion of LAA in patients in the observation group after 45 d and 6 months, respectively. Clinical outcomes in two groups were compared from the following aspects: recurrence of IS, incidence of systemic embolism, and the 3-year recurrence-free survival (RFS). The 3-year IS recurrence of patients was compared by Fisher’s exact test. Results. No significant differences were observed at baseline levels (age, sex, etc.) between the observation group and control group (
p
>
0.05
). During follow-up visit of 45 d and 6 months, all occluders met the efficacious occludsion criteria. The results of TEE at 45 d after LAAO showed that 50% of patients (30/60) in the observation group had complete occlusion of LAA. The results of TEE at 6 months after LAAO suggested that 58.3% of patients (35/60) had complete occlusion of LAA. IS recurrence in the observation group (3.33%, 2/60) was significantly lower than that in the control group (18.33%, 11/60), with the difference presenting statistical significance (
p
=
0.008
). Incidence of systemic embolism in the observation group (1.67%, 1/60) was markedly lower than that in the control group (13.33%, 11/60) (
p
=
0.014
). The average RFS in the observation group (31.97 months, 95% CI: 27.50~32.31 months) was notably longer than that in the control group (29.91 months, 95% CI: 29.85~32.92 months) (
p
<
0.05
). The 3-year IS recurrence of patients between two groups compared by Fisher’s exact test showed significant differences (1 year:
p
=
0.014
, 2 year:
p
=
0.008
, 3 year:
p
=
0.008
). Conclusion. Regarding patients with previous IS who had poor response to thrombolytics and anticoagulants, LAAO could effectively decrease recurrence of IS and incidence of systemic embolism and prolong RFS of patients. LAAO was, therefore, an alternative for patients with high IS recurrence risk.