The present study was conducted to compare aqueous nanoparticle-based Montanide™ IMS 1313 N VG PR (IMS 1313) and oil-based ISA 71 VG (ISA71) adjuvants in combination with an Eimeria subunit protein vaccine on protection against avian coccidiosis. Male broiler chicks were vaccinated twice with an Eimeria recombinant profilin protein alone or in conjunction with IMS 1313 or ISA 71 prior to infection with live, sporulated Eimeria acervulina oocysts. For comparison, chickens were immunized with a commercial live coccidiosis vaccine (Coccivac-B). The following parameters were assessed as measures of protective immunity: body weight gain, fecal oocyst output, profilin-specific intestinal secretary IgA (sIgA) or IgY antibody levels, and percentages of CD4(+), CD8(+), TCR1(+), or TCR2(+) intestinal intraepithelial lymphocytes (IELs). Birds vaccinated with profilin plus ISA 71 had increased body weight gains, equivalent to Coccivac-B vaccination, compared with the profilin-only group. Immunization with profilin plus IMS 1313, or with profilin plus ISA 71, reduced fecal oocysts shedding compared with the profilin-only group. Intestinal sIgA levels were greater in the profilin plus IMS 1313 or ISA 71 groups, and IgY levels were greater in the profilin plus ISA 71 group, compared with profilin alone. Birds vaccinated with profilin plus IMS 1313 or ISA 71 had higher percentages of CD4(+), CD8(+), and TCR1(+), but not TCR2(+), intestinal IELs compared with the profilin-only vaccinated group. Taken together, these results indicate that immunization of chickens with the recombinant profilin subunit vaccine in conjunction with IMS 1313 or ISA 71 adjuvants increases protective immunity against experimental E. acervulina infection.