Adjuvants are a key component in enhancing immunogenicity of vaccines and play a vital role in facilitating the induction of the correct type of immunity required for each vaccine to be optimally efficacious. Several different adjuvants are found in licensed vaccines, and many others are in pre-clinical or clinical testing. Agonists for TLRs are potent activators of the innate immune system and some, such as CpG (TLR9 agonist), are particularly good for promoting cellular immunity because of the induction of Th1 cytokines. Emulsions that have both delivery and adjuvant properties are classified as water-in-oil (W/O) or oil-in-water (O/W) formulations. The W/O emulsion Montanide ISA-51, often combined with CpG, has been widely tested in cancer vaccine clinical trials. Squalene-based O/W emulsions are in licensed influenza vaccines, and T-cell responses have been assessed pre-clinically. No clinical study has compared the two types of emulsions, and the continued use of W/O with CpG in cancer vaccines may be because the lack of single adjuvant controls has masked the interference issue. These findings may have important implications for the development of vaccines where T-cell immunity is considered essential, such as those for cancer and chronic infections. Using particulate (hepatitis B surface antigen) and soluble protein (ovalbumin) antigen, we show in mice that a W/O emulsion (ISA-51) abrogates CpG-mediated augmentation of CD8+ T-cell responses, whereas a squalene-based O/W emulsion significantly enhanced them.