Fifty-seven multiparous Awassi ewes in the breeding season were used to compare the effects of controlled internal drug release (CIDR) reuse on hormone profiles, reproductive performance, and economic production. Ewes were randomly allotted to one of three CIDR treatments: new (control), once-used, and twice-used; treatment lasted 12 days. Blood samples were collected from all groups at the time of CIDR insertion, three and six days following insertion, at withdrawal time, and at insemination. Serum estradiol (E2) and progesterone (P4) concentrations were measured. Timed insemination was performed 48 h post CIDR withdrawal in all groups. Pregnancy was diagnosed by ultrasonography at day 23 post insemination. No significant differences were detected among groups in pregnancy rate/ewes in heat, twinning rate, fecundity, abortion rate, and prolificacy. However, estrus detection rate was significantly higher in control (100%) than in other groups. The P4 concentration was significantly higher in control than in other groups during treatment period; at insemination, P4 concentration was significantly higher in control than in other groups; at insemination time, E2 concentration was significantly higher in control than in the other groups; and the net profit was higher in once-used than in other groups. One-time reuse of CIDR for the long term (12 days) can synchronize estrus in ewes efficiently with higher net profit than the new or twice-used CIDR.