Background: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors.Hypothesis: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs.Animals: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used.Methods: A prospective clinical trial in which dogs were treated with surgery alone (n 5 19) or also received adjuvant chemotherapy (n 5 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m 2 preceded by dexamethasone and diphenhydramine administration. Results: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P 5 .17), time to metastasis (P 5 .71), and overall survival (P 5 .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P 5 .009) and tumor fixation to underlying structures (P 5 .043, time to metastasis), as well as age (P 5 .018) and histologic stage (P , .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment.Conclusions and Clinical Importance: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.