We compared the efficacy of combination antiretroviral therapy (cART) of Antillean HIV-1-infected patients treated on the Caribbean island of Curaçao (CUR-AN) with Antillean (NL-AN), Surinam (NL-SUR), and Dutch (NL-NL) patients treated in The Netherlands. In total 2118 therapy-naive patients who started cART between January 2005 and August 2008 were included in the comparison. The CUR-AN patients initiated cART at a median CD4 cell count of 141 cells/mm(3) and 63% had counts below 200 cells/mm(3). Within 12 months of the start of cART 76% of the CUR-AN patients achieved viral suppression, defined as HIV-1 RNA plasma levels below 80 copies/ml. The percentage achieving viral suppression was higher in patients treated in The Netherlands (NL-AN = 87%, NL-SUR = 93%, and NL-NL = 96%). Lost to follow-up after 30 months of cART was 10% among CUR-AN patients and was higher than observed among patients treated in The Netherlands (NL-AN = 8%, NL-SUR = 3%, and NL-NL = 2%). A similar pattern was found for progression to AIDS and death (10% of CUR-AN vs. 5%, 6%, and 7% of NL-AN, NL-SUR, and NL-NL patients, respectively). Late start of cART and limited viral suppression after the start of cART determine the higher rate of disease progression to AIDS and death among Antillean patients treated in Curaçao. The high percentage of lost to follow-up may result in an underestimation of AIDS and AIDS-related death among HIV-1-infected Antilleans treated in Curaçao.