Angioimmunoblastic T-cell lymphoma (AITL) is a rare cancer of the lymphatic system. There is no effective chemotherapy regimen for long-term survival. The traditional chemotherapy regimen consists of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). This study evaluated the outcomes of a cyclophosphamide, doxorubicin, vincristine, prednisolone, and thalidomide (CHOP-T) regimen for patients with primary AITL. Clinical data of 48 primary AITL patients treated with CHOP-T or CHOP regimens were retrospectively analyzed. The 2-year overall survival (OS) and progression-free survival (PFS) rates of all patients were 52.8% and 36.6%, respectively. The 2-year OS rates of the CHOP-T group were better than that of the CHOP group (70.6% vs. 44.6%, P=0.045). However, this did not translate into significantly better PFS (P=0.122) or complete remission (CR) rates (P=0.068). Multiple-factor analysis showed that positive Coombs tests and bone marrow infiltration were independent prognostic factors of PFS. Only a positive Coombs test tended to be associated with lower OS rates. There were no statistically significant differences in hematologic toxicity between the two groups (P=0.299). Non-hematological toxicity in the CHOP-T group, such as diarrhea, peripheral neuropathy, and somnolence/fatigue, was significantly higher than in the CHOP group (P=0.017). The present study showed that the CHOP-T regimen was more effective than the CHOP regimen in improving OS and CR rates, but non-hematological toxicities were higher. Severity of diarrhea, peripheral neuropathy, and somnolence/fatigue was significantly associated with thalidomide and no efficient precautions were observed.