Objective：This study aims to explore the efficacy and safety of imatinib（IM）or nilotinib（NIL）as the first-line treatment in elderly chronic phase of chronic myeloid leukemia（CML-CP）. Methods：A retrospective analysis of 75 elderly CML patients receiving IM or NIL as first-line treatment. The clinical efficacy and safety indexes were compared between IM（43 cases）and NIL（32 cases）group. Results：No difference was found between the two groups when comparing 3 month-，6 month-，9 month- and 12 month- major molecular response（MMR）（23.07% vs. 15.00 %，52.38% vs. 52.38%，57.89% vs. 59.09%，54.17% vs. 57.14%，P＞0.05）and MR4.0（11.53% vs. 10.00 %，52.38% vs. 47.62%，57.89% vs. 50.00%，54.17% vs. 42.86%，P＞0.05）. There was no significantly difference of 3 month-，6 month-，12 month- and 18 month- optimal response between the two groups（60.47% vs. 75.00 %，60.47% vs. 71.88%，62.79% vs. 75.00%，72.09% vs. 90.63%，P＞0.05），as well as overall survival（OS），progression-free survival（PFS）and event-free survival（EFS）during the therapies（90.70% vs. 93.75%，79.07% vs. 90.62%，34.88% vs. 65.63%，P＞0.05）. More failure happened in IM group（15.63% vs. 44.19%，P=0.009）. More cardiovascular or hematologic adverse events（AEs） happened in NIL group（31.25% vs. 6.78%，P=0.006）. Conclusion：No difference was found between IM and NIL when comparing molecular response and optimal response. Less failure but more cardiovascular or hematologic AEs happened in NIL group.