Coronary artery disease (CAD) is the leading cause of death throughout the world. The aim of our study was to assess the role of 23 selected genetic risk factors and several clinical characteristics in overall survival of the patients suffering of chronic symptomatic three vessel disease (3VD) in 15-year follow-up study. Coronary angiography was performed in 810 consecutive subjects presenting with the symptoms of stable ischemic heart disease in the year 1998. Out of this number, 196 suffered of 3VD (>50% stenosis of LAD, LCx and RCA or their major branches). After exclusion of the patients treated for concomitant valvular disease, the rest was genotypized for 23 candidate polymorphisms covering PPAR-RXR pathway, matrix metalloproteinase-2, renin-angiotensin-aldosterone system, endothelin-1, cytokine genes, MTHFR and APO E variants. Data about 15-year survival were obtained from national insurance registry. All the data was available for 150 patients with 3VD. Statistical analysis used stepwise construction of Cox regression model assuming dominant, recessive or additive mode of genetic expression. Variables involved in each model construction included age, sex, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), diabetes mellitus (DM), ejection fraction (EF), left main stenosis, previously diagnosed stenosis of coronary artery, myocardial infarction in personal history and coronary bypass procedure, together with polymorphisms pre-selected by log-rank tests. Out of 23 polymorphisms, four (rs1536475, rs1800629, rs1800797 and rs1800795) have been included in the final model construction. SNP in IL-6 gene rs1800795 (-174 G/C) has been found to be a significant factor of survival in dominant and additive model, C allele associated with worse prognosis. This SNP was in linkage disequlibrium with rs1800797 (-597 G/A) in the same gene (D'=1.0; r2 = 0.97; p <10-20), which was also a significant predictor of survival when rs1800795 was not included in model construction. From other factors, age, BMI, diabetes, EF and left main stenosis were significant in all models. After adjusting for all clinical covariates and compared to GG carriers of rs1800795, CG carrirers had HR 2.20 (95% CI = 1.08–4.46) and CC homozygotes had HR 3.54 (95% CI = 1.67–7.53). Together with age, EF, BMI, diabetes and left main stenosis, the promoter variants in IL-6 gene were significant contributing factors to long term survival of the patients with chronic 3VD.