Contagious ecthyma or Orf is a common, contagious and zoonotic disease of small ruminants caused by orf virus. The present research was conducted to study the prevalence of Orf in and around Parbhani and to evaluate efficacy of different treatment against Orf in goat. Overall prevalence of Orf in goat was recorded 38.83%. The higher prevalence of Orf recorded in the kids below 4 months of age, male, poor health status and non-descript goats. The overall clinical signs in contagious ecthyma goats were pyrexia, severe proliferative ulcerated cauliflower-like lesions around lips and scabby lesions were commences on the lips, muzzles, mucocutaneous junctions, nostrils, ear, inner aspect of thigh and gums. The hematological parameters revealed erythrocytopenia, reduced hemoglobin, leukocytosis, neutrophilia and lymphopenia. For molecular confirmation, DNA extraction of all scab samples collected from suspected goats were showed amplification of partial B2L gene at 592 bp by PCR. Analysis of DNA sequence revealed that three Parbhani sequences were positive for CEV. The obtained 3 sequences of orf virus got accession numbers PP235095, PP235096 and PP235097 were closely related with each other and with other strains obtained from GenBank for the Parbhani district, Maharashtra and strains of other states of India mainly with Meghalaya, Assam and Goa. The present study concludes that aciclovir @ 10 mg/kg along with neem leaves extract and curcumin powder locally was effective in treating the CE in goats early as compared to other two groups.