Objective To determine the clinical efficacy of sustained release tablets of hydrochloride tramadol combined with pregabalin on the treatment of post-stroke thalamic pain in order to provide reference for clinical practice. Methods Forty patients with post-stroke thalamic pain admitted into our department from July 2010 to December 2014 were randomly divided into 2 groups, test group (tramadol and pregabalin, n＝22) and control group (tramadol alone, n＝18). Results Numerical Rating Scale (NRS) indicated that the pain level was significantly relieved in the test group after the treatment, and the relief was more significant than that of the control group. The effective rate and total effective rate of clinical treatment were significantly higher in the test group than in the control group (P＜0.05). Conclusion Combination of tramadol and pregabalin can effectively relieve the post-stroke thalamic pain and attenuate physical discomfort. Superior to simple tramadol, the treatment is of more ideal clinical efficacy and fewer adverse effects, and is worthy of clinical promotion.