Abstract: Objective To analyze the cost-benefit of clean needle and condom distribution comprehensive intervention among intravenous drug users (IDU) for the prevention of human immunodeficiency virus (HIV) infection and to provide references for the promotion of the program.Methods Data for the duration between August 2008 through August 2011 on capacity building among staff engaged in the intervention program,funding for propaganda and referral,number and person-times of IDU receiving medical service,number of clean needle and condom distributed,number of referrals,and characteristics of high risk behavior and change in HIV infection rate among target populations were retrospectively extracted from the dataset of HIV/AIDS Asia Regional Program (HAARP) in 19 counties of Yunnan province;then annual cost-benefit of the intervention program was evaluated.Results During the four years,204 backbone peers in 19 counties provided 394 321 services to 12 413 IDUs and totally 3 586 160 clean needles and 585 384 condoms were distributed;the number of referrals was 12 406 person-times;the total cost of the intervention measures was 9 058 398 Yuan (RMB).The increased HIV infection-related disability adjusted life years (DALY) among the target population were 5 144.7 persons-years.The total economic benefit contributed to the declined HIV infections was 59 515 776 Yuan; the net benefit was 50 460 378 Yuan; and the overall cost-benefit ratio of the intervention program was 1:5.6.Conclusion The clean needle distribution comprehensive intervention in Yunnan province achieves obvious cost-benefit and the intervention is of great significance for controlling the spread of HIV.