Objective To investigate safety and feasibility of percutaneous coronary intervention (PCI) via ipsilateral brachial artery approach for complex coronary artery lesions after unsuccessful radial artery puncture. Methods A retrospective study was conducted of 141 patients with complex coronary artery lesions, who were treated by PCI via femoral artery approach and brachial artery approach after unsuccessful radial artery puncture in Chinese PLA General Hospital from December 2014 to December 2017. They were divided into femoral group (n=83) and brachial group (n=58). The two groups were compared in success rate, incidence of com-plications, postoperative quality of life, and length of hospitalization. SPSS statistics 22.0 was used for statistical analysis. Student′s t test, Wilcoxon rank test, or Chi-square test was employed for comparison between groups. Results There was no significant difference in the operation time [(108.35±40.55) vs (104.33±43.57)min, P＞0.05] and success rate [(95.2%(79/83) vs 91.3%(53/58), P>0.05] between two groups. The brachial group, however, showed a lower incidence of complications (5.17%(3/58) vs 10.84%(9/83)], higher quality of life [(46.15±15.34) vs (33.00±18.01)score], milder anxiety [(51.22±30.11) vs (35.00±27.18) score], and shorter average hospitalization [(4.74±1.25) vs (2.52±1.09)d], the difference being statistically significant (P<0.05 for all). Conclusion PCI via brachial artery approach after unsuccessful radial artery puncture improves post-operative quality of life and psychological state of patients without compromising success rate.