Equine sarcoids are the most identified skin tumors of horses, which are highly associated with bovine papillomavirus infection. Sarcoids can impair the use of the horse and are difficult to treat, resulting in significant economic losses and a welfare concern. There is no vaccine available to protect global equines from sarcoids. We aimed to determine the safety and protective antibody response in horses immunized with a recombinant baculovirus vector vaccine expressing the L1 protein of bovine papillomavirus type 1 (BPV1). A group of 10 clinically healthy, sarcoid-free horses were immunized intramuscularly with 1 mL of the equine sarcoid vaccine in the neck twice at 3-week intervals. A control group of 5 clinically normal horses were immunized with culture medium. Clinical signs were monitored daily, while serum samples were collected from all horses before vaccination as well as periodically post-vaccination. All horses appeared normal clinically and no clinically relevant adverse reactions to vaccination were observed. Using a GFP-expressing pseudovirus based virus-neutralizing antibody assay, a robust neutralizing antibody response was detected in all immunized horses following two doses. Pre-vaccination serum from the vaccination group and serum samples from the control group had no detectable virus-neutralizing antibodies. All 10 vaccinated horses developed neutralizing antibody titers 40 to greater than 1280. As neutralizing antibodies are an established correlate of protection for BPV1, we anticipate that this vaccine could protect horses from sarcoids.