Abstract： Objective Adenoid cystic carcinoma (ACC), a rare malignancy in head and neck region, is predominately found in the salivary glands. Our study is to retrospectively analyze the treatment outcomes and prognostic factors of ACC originated from the major salivary glands. Methods A total of 54 patients diagnosed as ACC were treated in our institution, including 24 cases originated from the parotid gland and 30 from the submandibular or sublingual gland. According to the records, 26 patients received surgery alone and 28 were treated with surgery followed by radiotherapy with a median dose of 58 Gy (range, 50 -65 Gy). Results The Follow-up rate was 94%, and 15 patients from postoperative radiotherapy group and 20 from surgery alone group were followed up more then 5 years. The 5-year overall survival rate, local-regional control rate, distant metastasis rate, and disease-free survival rate were 97%, 71%, 13% and 69%, respectively. Lung metastasis, occurred in 7 patients, was the most common distant failure. Fifteen recurrences were observed, including 13 in surgery alone group and 2 in postoperative radiotherapy group. The 5-year local-regional control and disease-free survival rates were 90% and 85% for patients treated with postoperative radiotherapy, 54% and 55% for those treated with surgery alone. Univariate and multivariate analyses showed that postoperative radiotherapy was the only prognostic factor of local-regional control and survival rates. Other parameters such as nerve involvement did not significantly influence the treatment results. Conclusions Postoperative radiotherapy can improve the prognosis of ACC originate from the major salivary glands compared with surgery alone. Distant metastasis is an obstacle in curing the disease, which indicates the value of systemic treatment.