A study was conducted to examine the prevalence and epidemiological factors of a novel skin disease in giraffes inhabiting the Ruaha National Park (RNP). A cross-sectional drive-transect survey was conducted. Animals were observed using binoculars from the car. Potential epidemiological risk factors assessment included disease status, age, sex, disease severity, body condition, herd size, location, park zone, vegetation types, other wild animal species and presence of oxpeckers. The results showed that the prevalence of the skin disease was 79.8% and all areas of the park were affected. Adults animals were significantly more affected than sub-adults and young (P=0.001). Skin lesions were located on the forelimb of 98.6% (n=91) and nearly all (99%) of the skin lesions on affected giraffes appeared severe and chronic. Examination of other wild animal species in vicinity indicated that the disease is exclusive to giraffes animals. Grossly, lesions in affected animals comprised scabs, wrinkled skin and encrustations and dry or oozing blood. The study proposes to call the disease Giraffe Skin Disease (GSD). It was further recommended carrying out more and elaborate studies to determine the aetiological agent(s) and identify the risk factors associated with the GSD as well as assessment of long-term population impact and design mitigation measures.