To identify the risk factors associated with presentation for care with CD4 cell count ≤ 200 cells/mm(3) and death in HIV-infected patients in Lyon, France. Data were analyzed on participants from mid-1992 to December 2006 in the Lyon section of the French Hospital Database on HIV Infection. Patients were stratified into two categories according to CD4 cell count at first presentation for care in University of Lyon hospitals: Group 1 (Gr1) patients with CD4 ≤ 200 cells/mm(3) and Group 2 (Gr2) patients with CD4 >200 cells/mm(3). Multivariate logistic regression assessed the risk factors associated with first presentation for care with CD4 ≤ 200 cells/mm(3). Survival was analyzed according to the Cox regression model. Among 3569 eligible patients (838 females and 2731 males, mean age: 36.3 ± 10.3 years), 1139 (31.9%) were categorized as Gr1. The factors associated with first presentation for care with CD4 ≤ 200 cells/mm(3) were: older age, male gender, route of HIV transmission, migrant populations, geographical areas other than Rhône-Alpes, and access to care in 1992-1997. Overall mortality was higher in Gr1 than in Gr2 (24.4% [278/1139] vs. 4.1% [101/2430]; p<0.001). The risk of death was 5.81 [4.61-7.32] in Gr1 compared to Gr2. In addition to CD4 cell count, age and enrollment periods for care were factors independently related to death. Despite public health efforts in Lyon, one-third of HIV-infected patients reach the health care system with CD4 cell count ≤ 200 cells/mm(3), which was linked with higher mortality.