During the period studied, a total of 2,174 local zebu cattle were clinically examined and morbidity and mortality rates of 13.61% (296) and 4.97% (108) were recorded, respectively. Analysis of the active outbreaks revealed a relatively consistent morbidity rate, with the highest observed in Adama (15.38%), followed by Wenji (10.26%). The highest mortality rates were also observed in Adama (5.89%) and Wenji (3.42%). The LSD virus was isolated from 22 samples and all tested positive in polymerase chain reaction analysis. The disease was observed in the cattle regardless of previous vaccination with Kenyan sheep- and goat-pox vaccine; thus, vaccine efficacy was assessed under field conditions and the authors’ findings, together with a possible remedy, are presented in this paper.