The resistance profile and its correlation with mobile genetic elements were investigated in 11 Vibrio cholerae O1 and 2 Vibrio parahaemolyticus clinical isolates, as well as in 1 V. cholerae O1 and 1 V. cholerae non-O1 environmental isolate, isolated between 1991 and 1996 in different provinces of Angola. All clinical isolates of V. cholerae O1 were resistant to ampicillin, chloramphenicol, trimethoprim, sulfamethoxazole, and tetracycline. They also contained a large conjugative plasmid (p3iANG) with a set of three class 1 integrons harboring dfrA15, blaP1, and qacH-aadA8 cassettes, which code for resistance to trimethoprim, beta-lactams, quaternary ammonium compounds, and aminoglycosides, clustered in a 19-kb region. Chloramphenicol (cat1), kanamycin (aph), sulfonamide (sul2), and tetracycline (tetG) resistance genes were also carried on the plasmid within the same 19-kb region. A chromosomal integron containing the dfrA15 cassette was also revealed in V. parahaemolyticus strains. SXT integrase genes were present in six V. cholerae isolates but apparently were not associated with known SXT-associated resistance genes. This study indicates that plasmids and integrons contributed mainly to the circulation of multiple-drug resistance determinants in Vibrio strains from Angola.