A trial on Syrian hamsters () infected with serovar was established to compare treatment efficacies of daily intramuscular (i.m.) injections of either 10 mg/kg of 5% enrofloxacin (Baytril [BE]; Bayer Animal Health, Mexico) or the same dose of enrofloxacin hydrochloride-dihydrate (enro-C). Hamsters were experimentally infected via the oral submucosa with 400 microorganisms/animal, in a sequential time schedule aligned to the initial treatment day, and were treated in groups as follows: a group treated with 5% enrofloxacin daily for 7 days after 24 h of infection (group BE); a group treated as described for group BE but with enro-C (enro-C); a group also treated with 5% enrofloxacin but starting at 72 h after infection (BE); a group treated as described for group BE but with injection of enro-C (enro-C). An untreated-uninfected control group (group CG) and an infected-untreated control group (group CG) were assembled ( = 18 in all groups). Weights and temperatures of the hamsters were monitored daily for 28 days. After hamsters were euthanatized or following death, necropsy, histopathology, macroscopic agglutination tests (MAT), bacterial culture, and PCR were performed. The mortality rates were 38.8% in group BE and 100% in group BE No mortality was observed in group enro-C, and 11.1% mortality was recorded in group enro-C The mortality rates in groups CG and CG were 100% and zero, respectively. Combined necropsy and histopathologic findings revealed signs of septicemia and organ damage in groups BE, BE, and CG Groups enro-C and CG showed no lesions. Moderated lesions were registered in 3 hamsters in group enro-C MAT results were positive in 83.3% of BE hamsters (83.3%) and 100% of BE and CG hamsters; MAT results were positive in 16.7% in group Enro-C and 38.9% in group enro-C Only 4/18 were PCR positive in group enro-C and only 1 in group enro-C ( < 0.05). It can be concluded that enro-C may be a viable option to treat leptospirosis in hamsters and that this may be the case in other species.