The financial cost of clinical Lumpy Skin Disease (LSD) and the financial benefit of its control through vaccination were studied based on questionnaire survey in Oromia region of Ethiopia from the perspective of livestock farmers. Production loss impacts for local zebu cattle were compared with those of Holstein Friesian (HF)/crossbred cattle in the study area. Annual cumulative incidence of LSD infection in HF/crossbred and local zebu cattle were 33.93% (95% CI: 30.92-36.94) and 13.41% (95% CI: 12.6-14.25) respectively and significantly different (p < 0.05). Annual mortality was also significantly higher in HF/crossbred 7.43% (95% CI: 5.76-9.10) than in local zebu cattle 1.25% (95% CI: 0.98-1.52). The annual financial cost was calculated as the sum of the average production losses due to morbidity and mortality arising from milk loss, beef loss, traction power loss, and treatment and vaccination costs at the herd level. The financial cost in infected herds was estimated to be USD 6.43 (5.12-8) per head for local zebu and USD 58 (42-73) per head for HF/crossbred cattle. A partial budget analysis was used to estimate the financial benefit of an annual vaccination program in both the local zebu and HF/crossbred cattle farming systems. The marginal rate of return (MRR) gained from this control intervention was estimated to be 34 (3400%) and the net benefit per head was USD 1 for local zebu and USD 19 for HF/crossbred cattle. Vaccination thus enabled financial costs due to LSD to be reduced by 17% per head in local zebu herds and 31% per head in HF/crossbred herds. These results could provide guidance to producers and the government in their endeavors to control the disease.