Foot and mouth disease (FMD) is a highly transmissible viral disease of cloven-hoofed animals, which is endemic in many developing countries. Vaccination is the main tool for FMD control in resource limited endemic countries like Ethiopia. Vaccine quality, which is often questionable in developing countries, is a critical element for effective disease control. The present study was aimed at evaluating the field effectiveness of a trivalent FMD vaccine (containing serotypes O, A and SAT 2), produced and widely used in Ethiopia, in terms of preventing clinical infection and severe disease. A randomized controlled field trial design was employed in the study in which the attack rate of clinical FMD infection in vaccinated cattle was compared with the attack rate in unvaccinated controls in cattle population of 16 villages in Gondar Zuria district, Northwest Ethiopia. The vaccine was administered as a single dose course in the face of an impending FMD outbreak and the trial groups were monitored for clinical infection until the end of the outbreak. The attack rate of clinical FMD 20 days post vaccination in the vaccinated cattle (34 %) was significantly lower than the attack rate in the unvaccinated controls (49 %) (p < 0.001). However, the effectiveness of the vaccine was only 31 % (95 %CI: 20-40 %). This vaccine effectiveness increased to 52 % ((95 %CI: 33-66 %) 42 days post vaccination. The proportion of severely affected cattle in the vaccinated group (5.7 %) was significantly lower than in the unvaccinated group (9.4 %) (p < 0.001), resulting in 39 % (95 %CI: 18-55 %) vaccine effectiveness against severe disease. Generally, the observed level of vaccine effectiveness was lower than the internationally recommended 75 % plus expected percentage of protection for a standard potency 3PD/dose FMD vaccine. Moreover, the level of effectiveness was insufficient to provide herd immunity to control the disease at the population level. Nevertheless, given the significant difference in the incidence of clinical disease and severity between vaccinated and unvaccinated cattle, it might still be worth using the current vaccine to reduce production losses associated with the disease provided it is cost effective and affordable for the farmers. Factors that cause low effectiveness of the vaccine need to be identified and addressed for effective control of the disease at population level.Copyright © 2020 Elsevier B.V. All rights reserved.