Aim To investigate the role of aldehyde dehydrogenase-2 (ALDH-2) in the oxidized low density lipoprotein(ox-LDL) induced endothelial progenitor cells (EPC) apoptosis and its molecular mechanism. Methods EPC isolated from peripheral circulation of healthy adults were cultured, challenged with blank, 10 mg/L ox-LDL and 1 μmol/L Alda-1 (a ALDH-2 specific activator) pretreatment plus 10 mg/L ox-LDL and used to evaluate apoptotic rate with DAPI stain, reactive oxygen species (ROS) level with DCFH-DA, mitochondrial membrane potentials with JC-1, caspase-3 signal pathway with Western blot. Results The apoptotic rate of the blank group, ox-LDL treatment group and Alda-1 pretreatment plus ox-LDL treatment group were respectively 4.9%±0.4%, 17.9%±2.9% and 7.5%±0.8%,the difference was significant(P＜0.05, n=6). The proportion of EPC lost which their mitochondrial membrane potentials were respectively 3.6%±0.7%, 28.5%±5.3% and 12.4%±1.3% in the blank group, ox-LDL treatment group and Alda-1 pretreatment plus ox-LDL treatment group, the difference was significant(P＜0.05, n=6). The ROS levels were respectively 319.7%±23.5% and 152.7%±9.4% in ox-LDL treatment group and Alda-1 pretreatment plus ox-LDL treatment group compared to the blank group (P＜0.05, n=6). The Western blot results showed that ox-LDL increased caspase-3 expression, but the pretreatment of Alda-1 reduced the ox-LDL induced caspase-3 expression(P＜0.05, n=6). Conclusion ALDH-2 could reduce ROS level in EPC, stabilize mitochondrial membrane potentials of EPC and reduce EPC apoptosis. Otherwise these are related to caspase-3.