BACKGROUND We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of pregabalin for pain management following spine surgery. METHODS In September 2016, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. RCTs of patients prepared for spine surgery that compared pregabalin with placebo were retrieved. The primary endpoint was the VAS score with rest or mobilization at 12 hours, 24 hours, and 48 hours and cumulative morphine consumption at 24 hours and 48 hours. The secondary outcomes were complications of nausea, sedation, dizziness, headache, and visual disturbances. After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. RESULTS Ten clinical studies with 535 patients (pregabalin group = 294, control group = 241) were included in the meta-analysis. Pregabalin was associated with reduced pain scores at 12 hours, 24 hours, and 48 hours, corresponding to a reduction of 1.91 points (95% CI, -4.07 to 0.24 point) at 12 hours, 2.66 points (95% CI, -4.51 to -0.81 point) at 24 hours, and 4.33 points (95% confidence interval, -6.38 to -2.99 point) at 48 hours on a 100-point numeric rating scale. There was no significant difference between VAS scores with mobilization at 12 hours, 24 hours, or 48 hours. Similarly, pregabalin was associated with a reduction in cumulative morphine consumption at 24 hours (-7.07, 95% CI -9.84, -4.30) and 48 hours (-6.52, 95% CI -7.78, -5.25, P = 0.000). Furthermore, pregabalin can reduce the occurrence of nausea (RR 0.57, 95% CI 0.41, 0.79, P = 0.001, number needed to treat = 8.4). There were no significant differences in the occurrence of sedation, dizziness, headache, or visual disturbances. CONCLUSIONS Preoperative use of pregabalin was efficacious in reduction of postoperative pain, total morphine consumption, and the occurrence of nausea following spine surgery. Because the sample size and the number of included studies were limited, a multicenter RCT is needed to identify the effects and optimal dose of pregabalin for reducing acute pain after spine surgery.