Immunoblots remain the gold standards for HIV-1/HIV-2 infection confirmation. However, their ability to differentiate HIV-1 from HIV-2 infection on an antigenically diversified HIV-1 and HIV-2 panel remain scarce. We performed a multicenter study on 116 serum samples accounting for most HIV-1 (9 different subtypes in group M, 17 CRFs, 3 group O) and HIV-2 (groups A and B) diversity, evaluating seven confirmatory assays (six commercially available assays and one in-house assay) with genotyping as reference. The assays were INNO-LIA HIV I/II Score, HIV-2 Blot 1.2, HIV Blot 2.2, New Lav Blot I and II, Geenius and an in-house Serotyping ELISA. Among HIV-1 samples, INNO-LIA, HIV Blot 2.2, New Lav Blot I, Geenius and Serotyping had comparable high sensitivities, from 98% to 100%, whereas HIV-2 Blot 1.2 and New Lav Blot II had a high undetermined rate (85% and 95%, respectively). HIV-2 Blot 1.2 and New Lav Blot II misclassified 7% and 5% HIV-1 samples as HIV-2, respectively, and HIV-2 Blot 1.2 had a 8% false-negative rate. Among HIV-2 samples, INNO-LIA, New Lav Blot II, HIV-2 Blot 1.2 and Serotyping had high sensitivities, from 96% to 100%. HIV Blot 2.2 misclassified 17% HIV-2 samples as HIV-1/HIV-2 dual infections. New Lav Blot I misclassified 19% of HIV-2 samples as HIV-1 with a high (81%) undetermined rate, and Geenius misclassified 2% as HIV-1 and 7% as untypable HIV-positive. For HIV-1/HIV-2 dual infection, results were less sensitive with at most 87.5% for INNO-LIA and Geenius, and 75% for HIV Blot 2.2 and Serotyping. Overall, confirmatory assays remain useful for most cases, with the exception of HIV-1/HIV-2 dual infection suspicion.