Abstract Background Epidemiologic studies have evaluated the association between tumor necrosis factor-alpha (TNF-α) gene -308A/G polymorphism and the risk of acute pancreatitis (AP), but the results are inconsistent. In order to derive a more precise estimation of the associations, a meta-analysis was performed. Materials and methods Systematic searches of electronic databases PubMed, Embase, and Web of Science, as well as hand searching of the references of identified articles, were performed. All case-control studies investigating the association between TNF-α gene -308A/G polymorphism and AP risk were included. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. Results The initial search revealed 818 potentially eligible studies. Having read the title, abstract, or full text, we included six relevant studies in the final meta-analysis, which contained 1,006 AP cases and 782 controls. Overall, no significant association was found between TNF-α gene -308A/G polymorphism and AP risk when all studies were pooled into the meta-analysis (for A/A+A/G versus G/G: OR = 1.03, 95% CI = 0.83-1.28, P = 0.79; for A/A versus A/G+G/G: OR = 0.97, 95% CI = 0.65-1.45, P = 0.87; for A/A versus G/G: OR = 1.23, 95% CI = 0.79-1.91, P  = 0.37; for A allele versus G allele: OR = 0.99, 95% CI = 0.83-1.18, P = 0.90). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity and subtype of AP. Conclusions The present meta-analysis reveals that the TNF-α gene -308A/G polymorphism is not associated with AP risk. However, due to the small number of subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.