Coronary heart disease (CHD) is a well-established multifactorial disease. Inflammation and atherosclerotic lesions play a fundamental role in CHD progression. Interleukin-10 (IL-10), an anti-inflammatory cytokine has the potential to influence the development of CHD. Thus, the identification of variations in IL-10 gene might be beneficial for the early detection of CHD. The current study aimed to examine the role of IL-10 gene polymorphisms (rs1 800 896, rs1 800 871 and rs1 800 872) in association with CHD. After taking blood samples, DNA extraction was done followed by genotyping through tetra primer amplification refractory mutation system-polymerase chain reaction (tetra primer ARMS-PCR). Obtained results showed a significant difference in the genotypic distributions of rs1 800 896 (p < 0.001) and rs1 800 871 (p < 0.001). The obtained odds ratio (OR) with 95% confidence interval (CI) for rs1 800 896 revealed significant association with CHD (OR = 1.90, 95% CI 1.3-2.7, p < 0.001). Furthermore, dominant, co-dominant and recessive models of rs1 800 896 indicated a significant correlation with the elevated risk of disease. Whereas, for rs1 800 871, a decreased risk was detected (OR = 0.55, 95% CI 0.4-0.8, p < 0.01). Moreover, it has been observed that rs1 800 871 might play a protective role for CHD under co-dominant and recessive models. However, rs1 800 872 was not observed to be significantly associated with the genetic risk to CHD among the studied population. The acquired results suggested that rs1 800 896 and rs1 800 871 have a substantial relationship with CHD and rs1 800 896 may be used as a diagnostic biomarker for early detection of the disease.