Objective: To evaluate the effects of tube voltage on image quality in coronary CT angiography (CCTA), the estimated radiationdose, and DNA double-strand breaks (DSBs) in peripheral blood lymphocytes to optimize the use of CCTA in the era of lowradiation doses. Materials and Methods: This study included 240 patients who were divided into 2 groups according to the DNA DSB analysismethods, i.e., immunofluorescence microscopy and flow cytometry. Each group was subdivided into 4 subgroups: thosereceiving CCTA only with different tube voltages of 120, 100, 80, or 70 kVp. Objective and subjective image quality wasevaluated by analysis of variance. Radiation dosages were also recorded and compared. Results: There was no significant difference in demographic characteristics between the 2 groups and 4 subgroups in eachgroup (all p > 0.05). As tube voltage decreased, both image quality and radiation dose decreased gradually and significantly.After CCTA, γ-H2AX foci and mean fluorescence intensity in the 120-, 100-, 80-, and 70-kVp groups increased by 0.14, 0.09,0.07, and 0.06 foci per cell and 21.26, 9.13, 8.10, and 7.13 (all p < 0.05), respectively. The increase in the DNA DSB level inthe 120-kVp group was higher than those in the other 3 groups (all p < 0.05), while there was no significant difference inthe DSBs levels among these latter groups (all p > 0.05). Conclusion The 100-kVp tube voltage may be optimal for CCTA when weighing DNA DSBs against the estimated radiationdose and image quality, with further reductions in tube voltage being unnecessary for CCTA.