BackgroundNitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization.Methods and results200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm.ConclusionThe eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11033-023-08434-0.