Purpose: Pregabalin is a new neuropathic drug that gained recent popularity in treatment of acute postoperative pain. The purpose of this study is to study the effect of pregabalin in pain management in the first 24 h after total knee arthroplasty. Methods: PubMed, Scopus, EBSCO, and Web of science were searched for randomized controlled trials that study the effect of pregabalin in the management of pain after total knee arthroplasty. Pain scores at rest and with movement and opioid consumption in the first 24 h and the occurrence of adverse events were the primary outcome measure. The statistical software RevMan 5.3 was used to analyze the statistical significance of the results. Results: A total of 5 randomized controlled trials with 608 were collected. There was no significant benefit from the use of pregabalin in the management of pain in the perioperative period in patients undergoing primary total knee arthroplasty. Pain score after 24[Formula: see text]h at rest using 150 mg/day was (MD [Formula: see text]0.53, P value 0.23). Pain score after 24 h with movement using doses less than 300 mg/day was (MD [Formula: see text]1.11, P value 0.79). Opioid intake was not significantly reduced in patient taking pregabalin using doses less than 300 mg/day or doses higher than 300 mg/day (SMD [Formula: see text]0.42, 0.59. P value 0.10, 0.42, respectively). Most of studies observed increased occurrence of adverse events with the use of pregabalin. Conclusion: This study demonstrates that pregabalin does not decrease pain scores in the first 24 h after total knee arthroplasty while it increases the occurrence of side effects.