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Objective To investigate the effect of a treatment course of comprehensive intervention with Traditional Chinese Medicine (TCM) on the mortality of patients with acquired immunodeficiency syndrome (AIDS) treated with combined antiretroviral therapy (cART). Methods AIDS patients who had taken cART in a national TCM human immunodeficiency virus treatment trial program (NTCMTP) before 2009 were enrolled in this study and followed for 36 months from November 2009. Patients enrolled in the NTCMTP in 2004 were taken as the first group, those enrolled in 2006 as the second group, and those enrolled in 2009 as the third group. Cumulative survival rates were calculated by the life table method. Survival curves for subgroups were compared by the log-rank test. Hazard ratios were calculated with a Cox proportional hazards model. Results A total of 1443 AIDS patients were followed for 3 years (4198 person-years). During this period, 91 (6.3%) patients died and 13 (0.9%) were lost to follow-up. The total mortality rate was 2.17/100 person-years. The mortality rate of patients enrolled in the NTCMTP in 2004 was 1.49/100 person-years, which was lower than that of patients enrolled in 2006 (2.23/100 person-years) and 2009 (3.48/100 person-years). After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 + T-cell counts, and long-term treatment with cART were risk factors of mortality. Conclusion Long-term treatment with TCM decreased the mortality risk of AIDS patients. Factors such as being male, older age, CD4+ T-cell counts, and time of treatment with TCM and cART were correlated with mortality.