Background/aim: Scars develop at the end of the natural wound-healing process and are characterized by excessive collagen deposition, particularly types I and III collagen. This study aimed to investigate the genetic association of COL1A1 ?1997 G/T (rs1107946) and COL1A1 Sp1 +1245 G/T (rs1800012) polymorphisms with the incidence of scars. Materials and methods: A case-control association study was conducted with 84 volunteers from Jeddah, Saudi Arabia (47 patients and 37 controls). The allele frequency distribution and nucleotide genotypes of ?1997 G/T, +1245 G/T were ascertained by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Results: Our results indicated that the distribution of COL1A1 (rs1107946) genotypes was significantly different between patients and controls (P = 0.00). The incidence of COL1A1 (rs1107946) genotype GG was significantly associated with a risk of scars. The distribution of the (rs1107946) genotype was drastically higher in women with scars (P= 0.00). One haplotype block in COL1A1 was documented by the pair-wise linkage disequilibrium between the single nucleotide polymorphisms1397645907(SNPs). The frequency of the GG haplotype constructed by the two SNPs was robustly high and associated with risk of scars. Conclusion: Our results strengthen the evidence for the association between polymorphisms of ?1997 G/T, +1245 G/T of the COL1A1 gene in the genetic etiology of keloid scars.