Background: Keloid disease (KD) is common and often refractory to treatment. Definition of the genetic mechanisms of KD can lead to a better understanding of the disease and suggest more effective treatment strategies. Objectives: To quantitatively estimate the association between KD susceptibility and the -509C/T polymorphism in the TGF-β1 gene. Methods: PubMed, Embase and CNKI databases were searched using a combination of the Medical Subject Headings (MeSH) and relevant words in titles. Analyses were performed with STATA 12.0. Results: Five case-control studies encompassing a total of 564 keloid cases and 620 healthy controls were pooled in the final meta-analysis. Among the five studies, no significant association was detected between the TGF-β1 -509C/T polymorphism and KD under all of the five genetic models (allele comparison, heterozygote comparison, homozygote comparison, dominant model and recessive model) for the overall analyses and for the subgroup analyses based on DNA extraction method, participant ethnicity and group size. When stratified by study quality, three high-quality studies showed significant association under allele comparison and homozygote model (C versus T: OR = 0.80, 95% confidence interval [CI] = 0.65–0.98, P = 0.03; I 2 = 0%, P = 0.64; CC versus TT: OR = 0.62, 95% CI = 0.41–0.94, P = 0.02; I 2 = 0%, P = 0.79); while two moderate-quality studies showed significant association under allele comparison, homozygote model and recessive model (C versus T: OR = 1.52, 95% CI = 1.15–2.01, P = 0.004; I 2 = 39%, P = 0.20; CC versus TT: OR = 2.14, 95% CI = 1.24–3.70, P = 0.02; I 2 = 19%, P = 0.27; CC versus CT+TT: OR = 2.04, 95% CI = 1.29–3.24, P = 0.002; I 2 = 0%, P = 0.35). Conclusions: The current meta-analysis suggests that the TGF-β1 -509C/T polymorphism is not associated with KD susceptibility. High-quality and large-scale studies are needed to validate our findings.