Background and Objectives: Hypertension and diabetes are risk factors for coronary artery disease. The SYNTAX (synergy between percutaneous coronary intervention with taxus and cardiac surgery) score (SS) is a unique tool to score complexity of coronary artery disease. The aim of this study is to assess the independent and combined effect of hypertension and diabetes on SS score in patients underwent coronary angiography. Subjects and Methods: Total 2,163 patients underwent coronary angiography were enrolled. SS was calculated by using the SS algorithm which is available on the SS Website. The patients were divided into four groups: those without hypertension or diabetes (HT-/DM-), those with only hypertension (HT), only with diabetes (DM), and with hypertension plus diabetes (HT+/DM+). High SS was defined as SS ��� 10 according to median value of SS in overall patients. Multivariate analysis was performed using hypertension, diabetes, age, sex, body mass index, history of smoking, and level of serum hemoglobin, creatinine, c-reactive protein, high and low density lipoprotein cholesterol. Results: The median SS was 9.0 (5.0-17.0) for 885 patients with HT-/DM-, 9.0 (5.0-16.0) for 548 patients with HT, 10.0 (6.0-19.5) for 405 patients with DM and 13.0 (6.0-20.5) for 355 patients with HT+/DM+. Hypertension (odd ratio (OR) 0.912, 95% confidence interval (CI) 0.688-1.209) and diabetes (OR 0.94, 95% CI 0.686-1.289) were not associated with high SS. But combined hypertension and diabetes was an independent risk factor for high SS (OR 1.6; 95% CI 1.16–2.26). Conclusions: Coexistence of hypertension and diabetes results in a negative synergistic effect on SYNTAX score. Keywords: coronary artery disease, diabetes, hypertension, SYNTAX score