To study the natural history of HIV-1 infection among intravenous drug users (IDUs) detected in late 1989 in the study area and the factors related to survival of these IDUs infected with HIV. 196 injecting drug users first detected during August and December, 1989 were observed in Ruili county, Yunnan province. Data gathered from the 20-year follow-up program was collected and analyzed retrospectively. After 20 years' follow-up period, 90.3% of the 196 IDUs with HIV infection died, 5.1% of them were still alive, and 4.6% were lost. The crude pre-AIDS mortality rate was 98.1/1000 person-years, and the AIDS mortality rate was 54.9/1000 person-years. Malaria, septicemia were the main causes of death among the natural diseases whereas overdose and accidental causes were the principal causes related to those non-disease deaths. The median survival time from sero-conversion to death was 8.6 years (95%CI: 7.6 - 9.7). The median survival time from sero-conversion to death due to AIDS was 11.3 years (95%CI: 10.3 - 12.8) with the incubation time as around 10.3 years. People older than 30 years at seroconversion and length of drug usage were associated with shorter survival time, with hazards ratios as 1.9 and 0.7, respectively. A high pre-AIDS mortality was observed among IDUs. Both the median survival time from sero-conversion to death and the HIV incubation period were shorter than that observed in the developed countries. Age of HIV infection seemed to have a strong effect on survival.