Background: Depression and anxiety are common after stroke. There is inconclusive evidence of the benefit of psychotherapy for poststroke depression and anxiety. Here, we used a brief intervention, Neuro-Linguistic Programming (NLP) brief therapy plus health education, to evaluate the changes in patients with ischemic stroke. Methods: One hundred eighty patients were randomly allocated to receive 4 sessions of NLP plus health education (n = 90) or usual care (n = 90). A set of questionnaires was used preintervention and postintervention as well as at the 6-month follow-up. The primary outcomes were the prevalence of depression and anxiety, and the awareness of stroke knowledge. Results: More patients in the intervention group achieved remission of depressive (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.41-5.59) and anxious symptoms (OR, 2.19; 95% CI, 1.15-4.18) after intervention. At the 6-month follow-up, we found no differences between groups in both the prevalence of depression and anxiety. After intervention, the intervention group had better awareness rates on most of the stroke knowledge items (P < .05). It also had better quality of life and physical function both after intervention and at the follow-up (P < .05). Conclusions: NLP plus health education could reduce depression and anxiety immediately after intervention, but not at the 6-month follow-up. The intervention could also improve the awareness of stroke knowledge and benefit patients on quality of life and physical function.