Background: Post-stroke fatigue (PSF) is a major, frequently sequela of stroke. Evidences have shown that PSF is an unfavorable condition for stroke rehabilitation and neurological functional recovery. Chinese herbal medicine (CHM) has been used for centuries in China to treat stroke patients, however, few studies have confirmed the effectiveness of CHM using the western clinical evaluation approach. Objective: The aim of this study was to evaluate the therapeutic effect of modified BuYangHuanWu decotion(BYHWD) and explore its clinical evidence on PSF in a 4-week randomized controlled trial. Methods: Ninety-two PSF patients were included in a randomized and controlled trial. Patients were randomly divided into active treatment group with BYHWD(n=47) or control group (n=45). All the patients received routinized rehabilitation treatments and medications. Fatigue Severity Score (FSS), Visual Analogue Fatigue Scale (VAFS) and Modified Barthel Index (MBI) were used to evaluate the fatigue level of all patients. Results: The mean age of the participants was 63.07 years and 42 (46 %) were women. The BYHWD group showed significant reduction on the FSS, VAFS in comparison with that in the control group after treatment (p < 0.05), however, the changes of MBI scores between two groups had no difference after treatment (p > 0.05). Conclusion: We concluded that the integration of BYHWD and conventional rehabilitation based on western medicine can be more effective on alleviating the symptoms of PSF. It has potentials improve patients' quality of life. More empirical studies with larger sample size are necessary to confirm the BYHWD's effectiveness on PSF. © 2016 IEEE.