Background: Different Matrix metalloproteinases (MMPs) family members may be implicated in acne vulgaris development. However, there are no published data about the role of MMP-1 and TIMP-1 gene polymorphisms in acne vulgaris development. Aims: To evaluate the association between MMP-1 (519 A/G) and TIMP-1 (372 T/C) gene polymorphisms and the risk of developing acne vulgaris among a sample of Egyptian acne patients. Patients/Methods: This case-control study included 100 acne vulgaris patients and 120 apparently healthy control subjects. Acne severity was assessed according to Global Acne Grading System (GAGS). MMP-1 (519 A/G) and TIMP-1 (372 T/C) gene polymorphisms were investigated using RFLP-PCR technique. Results: The MMP-1 (519 A/G) AG and GG genotypes and G allele increase the risk of acne vulgaris~2–3 folds. In female patients, TIMP-1 (372 C/T) TT genotype and T allele showed significantly higher frequency in cases compared with the control group (p = 0.004, 0.001 respectively) with a higher risk to develop acne. On the other hand, in male patients, there was insignificant difference between the frequency of alleles in patients and control subjects. TIMP-1 (372C/T) TT genotype has been shown to be significantly detected in the studied female patients associated with the positive family history of the disease, and it increases the risk of back affection, severe acne grade development, and the liability to postacne scar formation. Conclusion: MMP-1 (519 A/G) and TIMP-1 (372 T/C) gene polymorphisms may be related to acne vulgaris development.