Coronary artery disease (CAD) is a multifactorial disorder that results from an excessive inflammatory response. Secretory phospholipase A₂-V (sPLA₂-V) encoded byPLA2G5gene promotes diverse proinflammatory processes. The aim of the present study was to analyze ifPLA2G5gene polymorphisms are associated with premature CAD. ThreePLA2G5polymorphisms (rs11573187, rs2148911, and rs11573191) were analyzed in 707 patients with premature CAD and 749 healthy controls. Haplotypes were constructed after linkage disequilibrium analysis. Under dominant, recessive, and additive models, the rs11573191 polymorphism was associated with increased risk of premature CAD (OR = 1.51,P_dom= 3.5 × 10⁻³; OR = 2.95,P_rec= 0.023; OR = 1.51,P_add= 1.2 × 10⁻³). According to the informatics software, this polymorphism had a functional effect modifying the affinity of the sequence by the MZF1 transcription factor.PLA2G5polymorphisms were in linkage disequilibrium and theCGAhaplotype was associated with increased risk of premature CAD (OR = 1.49,P= 0.0023) and with hypertension in these patients (OR = 1.75,P= 0.0072). Our results demonstrate the association of thePLA2G5rs11573191 polymorphism with premature CAD. In our study, it was possible to distinguish one haplotype associated with increased risk of premature CAD and hypertension.