The objective of our study was to assess the association of eNOS4 and eNOS296 polymorphisms of endothelial nitric oxide synthase (eNOS) gene with obstructive sleep apnea syndrome (OSAS). Forty-eight patients with OSAS and 181 healthy volunteers were included in the study. Genotype analyses were performed for eNOS intron 4 VNTR and exon 7, Glu298Asp (G -> T) polymorphisms. There was no significant difference between the patients and controls regarding eNOS4 polymorphism (P > 0.05). There was a significant difference between the patients and controls regarding eNOS296 polymorphism. Glu/Asp variant was more frequent whereas Glu/Glu variant was less frequent in the patients compared to controls (P < 0.001). There was no relationship between eNOS4 and eNOS296 polymorphisms and polysomnography parameters, apnea-hypopnea index, age, gender, body weight and height, body mass index, hypertension, coronary artery disease, arrhythmia, diabetes mellitus, hypercholesterolemia and smoking (P > 0.05). The eNOS4 polymorphism of NOS gene is not associated with OSAS. However, eNOS296 polymorphism of NOS gene is associated with occurrence of OSAS, but not with severity of OSAS.