OBJECTIVE: The project was scheduled as a case-control study to investigate the correlation between MMP-2 (rs243864), MMP-9 (3918242), MMP-12 (rs7123600) and TIMP-2 (rs8176329) polymorphisms and chronic venous disease (CVD) risk. The genotype and phenotype research envisages the testing of possible associations between MMP and TIMP-2 genotypes and phenotypes of CVD. MATERIAL AND METHODS: 150 patients with CVD and 227 controls were enrolled into the study. The MMPs and TIMP-2 genotypes were identified by the PCR method and restriction analysis according to standard protocols. RESULTS: The G allele of MMP-2 -790 T/G was 1.85 times more frequent in men with CVD than in the control group (P = 0.008). The T allele of MMP-9 -1562 C/T was observed 2.571 times more frequently in patients with CVD than in the control individuals (both in men and women) with clinically significant specificity (P = 0.0000009). The G allele of MMP-12 rs7123600 was determined 2.082 times more frequently in female patients with CVD than in the control group with clinically significant specificity (P = 0.02). No significant result in TIMP-2 rs8176329 polymorphism in the case-control study was observed. CVD women with G allele in MMP-2 -790 T/G in the genotype-phenotype study are seen to develop ulceration 2.539 times more frequently (P = 0.003). The G allele of MMP-12 rs7123600 was detected 3.167 times more frequently in CVD women with ulceration compared with CVD women without ulceration (P = 0.007). In CVD men in C6 stage, the incidence of AG genotype in rs7123600 MMP-12 polymorphism was found to be 4.675 times higher compared to CVD women with C6 staging (P = 0.005). The AG genotype in TIMP 2 rs8176329 polymorphism was found to be associated with higher risk of tumour (P = 0.01). CONCLUSION: Studying these polymorphisms can contribute to better identification of patients at higher risk of developing CVD, while providing the most appropriate prevention and treatment strategies.