The aim of this study was to evaluate the efficacy of controlled internal drug release (CIDR) and its reuse in treatment of inactive ovaries in buffaloes with subsequent resumption of cyclicity and reduction of inter-calving intervals. This study was conducted on 54 anestrous buffaloes suffering from ovarian inactivity. The animals were treated by new CIDRs and disinfected second used CIDRs for 7 or 14 days and PGF2α, with or without GnRH. The highest estrus induction rate (EIR; 100%), pregnancy rate (PR; 100%) and 1st service conception rate (1st service CR; 83.3%) were achieved with the treatment regime (CIDR 7 days plus i.m. injection of 25 mg of PGF2α in the 6th day plus i.m. injection of 10 µg GnRH in 8th) day followed by the treatment regime (CIDR 14 days plus i.m. injection of PGF2α in the 13th day); where the EIR, PR and 1st service CR were 85.7, 71.4 and 57.1%, respectively. It could be concluded that the use of CIDR 7 days + i.m. injection of 25 mg of PGF2α in the 6th day + i.m. injection of 10 µg GnRH in 8th day is an alternative to restart the ovarian activity in buffalo cows