Virulent footrot is a significant economic and animal welfare concern. The disease can be treated, controlled, and eliminated with vaccine, but selecting the appropriate vaccination strategy can be challenging. There are two main strategies: outbreak (serogroup)-specific univalent or bivalent vaccination, or use of a multivalent vaccine containing up to nine of the most common serogroups. The objective of this study was to compare these approaches in sheep flocks infected with multiple Dichelobacter nodosus serogroups. In the first phase, we undertook an immunogenicity trial in which we compared four pre-commercial multivalent recombinant fimbrial vaccines containing six (A, B, C, G, H, I) or nine (A, B, C, D, E, F, G, H, I) serogroups, and compared them to commercial bivalent vaccines. Two multivalent vaccines stimulated significantly higher antibody responses than two other multivalent vaccines but the number of serogroups included in the multivalent vaccine formulations did not have a significant effect. In the first phase, we also compared inter-vaccination intervals of two- and three-months between sequential bivalent vaccines, and found that a two-month interval was sufficient to avoid antigenic competition. In the second phase, the most immunogenic multivalent vaccine (nine serogroups) was compared to sequential bivalent vaccines and monthly foot-bathing in a field trial in four commercial Merino flocks. The duration of protection afforded by the multivalent vaccine was likely to be less than that of the bivalent vaccines, as the antibody titres stimulated were lower and less persistent.