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This study was conducted in and around Debre Zeit town to assess the field efficacy of LSD vaccine in use and overview associated disease impact. The study comprised cross-sectional and retrospective study design which employed active disease follow-up, semi-structured questionnaire survey and molecular techniques. The finding revealed that the Kenyan sheep pox vaccine strain used for the control of LSD did not confer expected protection. From the total of 476 animals observed, 22.9% and 2.31% cattle were found sick and dead due to LSD, respectively. Breed specific morbidity rate was 22.5% in Holstein Friesian–zebu cross and 25.9% in local zebu breed. The disease was observed to be more serious in young animals and also in females. A trend of seasonality was also observed in its occurrence. The study finding urges the need for investigation of vaccine failure including vaccine matching and …