Abstract The diagnosis of HIV-1 is increasing in African-born persons residing in Europe. They present a high prevalence of HIV-1 non-B variant infections and of parasitic infections, both of which are infrequent in Western countries. Immigration favors their presence in nonendemic countries. In this study, all newly HIV-diagnosed individuals at an HIV/AIDS and Tropical Medicine reference center in Madrid from 2005 through 2007 were retrospectively studied. HIV-1 subtyping was performed in gag, pol, and gp41 coding regions by phylogenetic analyses. The presence of other pathogens was also evaluated. Furthermore, all HIV-1-infected Africans were screened for parasitic infections. Newly diagnosed HIV-1 subjects included 90 sub-Saharan Africans and 188 non-Africans (116 Spaniards, 13 other Europeans, and 59 Latin Americans). Significantly higher numbers of HIV-1-infected Africans than non-Africans were females, acquired HIV-1 by heterosexual contact, and presented a more advanced clinical CDC stage and criteria for starting antiretroviral therapy in the first clinical visit. They predominantly carried non-B subtype infections, mainly intersubtype recombinants. Half of HIV-1-infected Africans had parasitic infections. CD4(+) T cell counts were lower among Africans than Europeans at the time of HIV-1 diagnosis. At 12 months of follow-up after starting antiretroviral treatment, a significantly lower proportion of Africans than non-Africans achieved undetectable viremia due to their higher loss to follow-up. However, CD4(+) T cell recovery and virological failure rates were similar. Therefore, the profile of African HIV-1-infected immigrants varies widely with respect to Spanish HIV-infected individuals. More advanced immunodeficiency and the coexistence of parasitic diseases and infections with a large diversity of HIV-1 non-B and recombinant variants are expected.