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Depending on the type of injury, the pain mechanisms are multifactorial. Preoperative pregabalin administrations as an adjunct to a multimodal postoperative pain management strategy have been tested in various surgical settings. The purpose of current study was to evaluate the effects of preoperative pregabalin administration on postoperative pain intensity and rescue analgesic requirement following video-assisted thoracoscopic surgery (VATS).Sixty adult patients undergoing VATS were randomly assigned either to receive pregabalin 150 mg (Pregabalin group) or placebo (Control group) 1 hour before anesthesia. Primary efficacy variable was pain intensity. Secondary efficacy variables were the requirement of rescue analgesics, total volume of intravenous patient-controlled analgesia (IV-PCA), and adverse effects induced by pregabalin or IV-PCA.Pain intensity scores at post-anesthesia care unit (PACU), 6 and 24 hours were lower significantly in the Pregabalin group compared with the Control group (mean [SD]; 5.6 [2.0] vs 6.8 [1.8]; mean difference: 1.2, 95% CI of difference: 0.2166–2.1835, P = .018, mean [SD]; 3.8 [1.9] vs 5.6 [1.4]; mean difference: 1.8, 95% CI of difference: 1.0074–2.7260, P = .001 and mean [SD]; 2.6 [1.6] vs 3.5 [1.5]; mean difference: 0.9, 95% CI of difference: 0.0946–1.7054, P = .029, respectively]. Also, the frequency of additional rescue drug administered at PACU (median [interquartile range]; 2 [2–3] vs 1 [1–2], P = .027) was significantly less in the Pregabalin group. The incidences of adverse effects related to pregabalin or IV-PCA were not different between the groups.A single administration of pregabalin 150 mg before VATS decreased postoperative pain scores and incidence of additional rescue analgesics in the immediate postoperative period without increased risk of adverse effects.