Proinflammatory interleukin-18 (IL-18), high-sensitivity C-reactive protein (hS-CRP), tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory IL-10 are involved in the pathogenesis of atherosclerosis. The aim of this study was to determine the imbalance between pro- and anti-inflammatory cytokines in premature coronary artery disease (PCAD) and their association with the degree of angiographic atherosclerotic blockade. A case-control study was carried out at the National Institute of Heart Diseases, Rawalpindi, Pakistan. Three hundred eighty-five stable coronary artery disease patients aged <45 years were screened. A total of 172 subjects participated in this study, comprising 98 PCAD patients and 74 angionegative controls. Serum IL-10, IL-18, and TNF-alpha were measured using enzyme-linked immunosorbent assay and hS-CRP was analyzed using Immulite 1000. The mean age of the patients was 40 ± 4.23 years (69 men and 9 women). Serum IL-18, TNF-alpha, hS-CRP, and IL-18/IL-10 ratio were significantly raised in PCAD patients (P<0.01), whereas IL-10 was moderately increased (P<0.05) when compared with controls. Serum IL-18 and hS-CRP were significantly raised in patients with 86%-100% stenosis (n=57) when compared with patients with 71%-85% stenosis (n=41) (P<0.05). Serum IL-18, TNF-alpha, IL-18/IL-10 ratio, and hS-CRP significantly correlated (P<0.01) with the degree of angiographic blockade. Pro/anti-inflammatory cytokines play a vital role in the pathogenesis of PCAD and have potential to identify the degree of atherosclerosis.