Globally, 113 million new chlamydial infections occur each year. Antibiotics have not halted this epidemic and an effective vaccine is recognized to be the best means of reducing the incidence of pelvic inflammatory disease, ectopic pregnancy and infertility in women. Using the mouse model of chlamydial infection, the potential of NanoStatTM, an oil-in-water nanoemulsion adjuvant, in combination with the chlamydial major outer membrane protein (MOMP) was investigated. Female BALB/c mice were vaccinated intranasally and then challenged with C. muridarum to determine vaccine effectiveness against infection and pathology. Intranasal immunization (IN) resulted in high MOMP-specific IgG and IgA antibody titers in serum and vaginal lavage as well as strong splenocyte proliferation as determined by CFSE assay. Splenocytes from immunized mice secreted high levels of IFNγ, TNF-α and IL-17A, which are essential for protective immunity against chlamydial infection. Mice that were immunized with NanoStatTM and 20ug MOMP cleared infection faster and had 80% reduced incidence of oviduct occlusion (hydrosalpinx) compared to PBS immunized controls. Using a unique combination of 3 antigens, targeting different stages of the chlamydial life cycle, IN immunization reduced oviduct occlusion by 90%, even though infectious burden was only reduced by 25-30%. Interestingly, intramuscular immunization with the same antigen combination mixed with a second generation nanoemulsion adjuvant reduced infectious burden by >80% but only reduced oviduct occlusion by 50%. These data highlight the potential of NanoStatTM adjuvants for preventing genital chlamydial infections and further support our findings that inflammatory damage is not related to infectious burden.