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This study was carried out during breeding season on 125 repeat breeding buffaloes to evaluate the therapeutic efficacy of various hormonal and non-hormonal drugs in improving their reproductive efficiency. Repeat breeding buffaloes (112) were treated parenterally with 5 different drugs, keeping 13 animals as untreated control, and results were compared with 22 normal cyclic buffaloes. The conception rates in treatment cycle and overall of 3 cycles post-treatment were compared between different groups. For 25 and 32 repeat breeding buffaloes treated with 0.02 mg Gonadotropin Releasing Hormone (GnRH; Receptal 5 ml i/m), just after artificial insemination (AI) and 500 mg of hydroxy-progesterone caproate (Duraprogen 2 ml i/m) on day 4th or 5th postAI, the conception rates (CRs) in the treatment cycle were 60.00 and 43.75% and overall CRs within 3 cycles were 76.00 and 62.50% (P<0.05), respectively, with a mean treatment to fertile oestrus interval of 6.58±3.27 and 8.25±3.28 days. For 26, 23 and 6 repeating buffaloes treated with Enrofloxacin (Inj. Bayrocin single shot 30 ml) i/m at the time of AI, Ceftriaxone (Inj. Vetacef 2 g) intrauterine (i/ut) at 12-24 h post-AI, and Povidone plus Metranidazole (Ranvidone 20-40 ml) i/ut for 2-4 days (AI in next cycle), the first service conception rates were 23.08, 34.78 and 33.33%, respectively, and overall CRs 53.85, 65.22 and 83.33% (P<0.01), with the fertile oestrus intervals of 20.86±5.53, 12.20±4.49 and 17.20±8.17 days, respectively. The results of cefriaxone were better as compared to enrofloxacin. The overall CRs for the GnRH, progesterone and antibacterial therapies were 76.00, 62.85 and 53.85 to 83.33% (P<0.01), respectively (normal cyclic group 81.82%, repeat breeding control 38.46%), with significantly (P<0.05) shorter fertile oestrus interval in GnRH and progesterone treated groups as compared to antibiotics treated one. Thus, all these regimes, and GnRH in particular, are recommended to the practitioners for their use in the field to ameliorate the problem of repeat breeding in buffaloes.