The present study aimed to investigate the association of $$\hbox {g}.313\hbox {A}{>}\hbox {G}$$ g . 313 A > G and $$\hbox {g}.341\hbox {C}{>}\hbox {T}$$ g . 341 C > T polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north Indian population. In the present case–control study, CAD patients ( $$n = 200$$ n = 200 ) and age-matched, sex-matched and ethnicity-matched healthy controls ( $$n = 200$$ n = 200 ) were genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotype distribution of $$\hbox {g}.313\hbox {A}{>}\hbox {G}$$ g . 313 A > G and $$\hbox {g}.341\hbox {C}{>}\hbox {T}$$ g . 341 C > T polymorphisms of GSTP1 gene was significantly different between cases and controls ( $$P = 0.005$$ P = 0.005 and 0.024, respectively). Binary logistic regression analysis showed significant association of A/G (odds ratio (OR): 1.6, 95% CI: 1.08–2.49, $$P = 0.020$$ P = 0.020 ) and G/G (OR: 3.1, 95% CI: 1.41–6.71, P $$=$$ = 0.005) genotypes of GSTP1 $$\hbox {g}.313\hbox {A}{\!>\!}\hbox {G}$$ g . 313 A > G , and C/T (OR: 5.8, 95% CI: 1.26–26.34, $$P = 0.024$$ P = 0.024 ) genotype of GSTP1 $$\hbox {g}.341\hbox {C}{>}\hbox {T}$$ g . 341 C > T with CAD. The A/G and G/G genotypes of $$\hbox {g}.313\hbox {A}{>}\hbox {G}$$ g . 313 A > G and C/T genotype of $$\hbox {g}.341\hbox {C}{>}\hbox {T}$$ g . 341 C > T conferred 6.5-fold increased risk for CAD (OR: 6.5, 95% CI: 1.37–31.27, $$P = 0.018$$ P = 0.018 ). Moreover, the recessive model of GSTP1 $$\hbox {g}.313\hbox {A}{>}\hbox {G}$$ g . 313 A > G is the best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95% CI: 1.11–4.92, $$P = 0.020$$ P = 0.020 ). In conclusion, statistically significant associations of GSTP1 $$\hbox {g}.313\hbox {A}{>}\hbox {G}$$ g . 313 A > G (A/G, G/G) and $$\hbox {g}.341\hbox {C}{>}\hbox {T}$$ g . 341 C > T (C/T) genotypes with CAD were observed.