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Comparative therapeutic efficacy of three drugs; homeopathic complex, herbal (Neem seed extract) and antibiotic in the treatment of subclinical mastitis in dairy buffaloes was evaluated. Thirty six Surf Field Mastitis Test (SFMT) positive lactating animals were randomly divided into four equal groups named A, B, C and D. Group A was treated with homeopathic complex (Mastitojin GoldTM), Group B was treated with hydro-methanolic extract of Neem seeds (Azadirachta indica), Group C was treated with Procaine Penicillin and Group D was kept as untreated control. Bacteriological cure rate, milk pH, milk yield, cost effectiveness and SFMT cure rate were evaluated in groups. The pH was significant (P<0.01) in Group C at 7th and 14th day post treatment. Percent cure rates of mastitic quarters on the basis of SFMT was highest in Group C followed by Group B, Group A and Group D at 28th Day Post Treatment (DPT), respectively. The quarter based bacteriological cure rate was highest in Group C (83.33%) followed by Group B, Group A and Group D. Total milk yield of Group B was improved significantly (P<0.05) at 28th DPT as compared to other treatment groups. Comparison of treatment cost showed that neem seed extract is the cheapest source in the treatment of subclinical mastitis in dairy buffaloes. It was observed that the antibiotic therapy was better than the herbal (neem seed extract) therapy and homeopathic complex therapy.