To investigate the value of the results of transvaginal color Doppler ultrasound (TVCDU) combined with the serum carbohydrate antigen 199n (CA199) level for differential diagnosing uterine leiomyoma and adenomyosis. Methods: The clinical data of 174 patients with uterine diseases confirmed by postoperative pathology from January 2017 to December 2019 were selected. These patients were given TVCDU examination and the serum CA199 level detection, which included 101 cases with uterine fibroids in group A and 73 cases with adenomyosis in group B. The value of TVCDU combined with the serum CA199 level of the patients for differential diagnosing the uterine leiomyoma and the adenomyosis was analyzed by four grid table. Results: In group A, 86 patients were definitely diagnosed as uterine fibroids and 15 cases were misdiagnosed. In group B, 64 patients were definitely diagnosed as adenomyosis and 9 cases were misdiagnosed. The serum CA199 level (31.84±7.39) and the positive rate (40.6%) of the patients in group B were significantly higher than those (25.92±6.14 U/mL and 86.3%) of the patients in group A (P<0.05). The sensitivity, the specificity, and the accuracy of TVCDU for differential diagnosing uterine fibroids and adenomyosis were 87.6%, 85.2%, and 86.2%, respectively. The sensitivity, the specificity, and the accuracy of TVCDU combined with serum CA199 level for differential diagnosing uterine fibroids and adenomyosis were 93.2%, 92.1%, 92.5%, specificity, which had increased significantly. Conclusion: TVCDU combined with serum CA199 level for differential diagnosing uterine fibroids and adenomyosis has higher efficiency, which can provide important reference value for selecting the operative method before operation.