French Guiana is the region of France where the HIV epidemic is most prevalent. To determine the risk factors for being lost for follow-up, we followed a cohort of 1,213 patients between 1992 and 2002 and determined which variables were related to two definitions of being lost to follow-up: permanently disappearing from HIV clinics and coming back after more than 1 year of missed appointments. The incidence rate for permanent follow-up interruption was 17.2 per 100 person-years. The median time to lost to follow-up was 4.3 years (interquartile range = 1.4-8.4 years). Cox modeling showed that the younger age groups, foreigners, patients with initial CD4 counts at the time of HIV diagnosis less than 500/mm3, and patients followed before the availability of highly active antiretroviral therapy (HAART) were significantly more likely to be permanently lost to follow-up, suggesting that some of the patients may have died. When looking at temporary loss to follow-up, younger age groups, untreated patients, patients consulting before the availability of HAART, and patients with CD4 counts more than 500/mm3 were more likely to not come back for a period of more than 1 year.