Abstract Background Human brucellosis is an infectious multisystem disease that varies in severity and clinical course. Bacteremia in brucellosis is common; however, data on epidemiology and management of Brucella bacteremia are scarce. The World Health Organization recommends using doxycycline with rifampicin or an aminoglycoside for brucellosis. This study aims to compare the efficacy of the two treatment regimens (oral doxycycline/rifampicin or ciprofloxacin versus IV gentamicin plus oral doxycycline/rifampicin or ciprofloxacin) in Brucella bacteremia. Methods In this single-center, retrospective cohort study, we analyzed the outcomes of 93 adults with confirmed Brucella bacteremia from 2017 to 2020. The diagnosis of brucellosis was based on positive blood culture for Brucella species. The patients were divided into two cohorts according to the treatment regimen received (oral versus IV). Blood culture negativity after four weeks and clinical cure rate at end of therapy were the co-primary endpoints, while side effects were secondary endpoints. Fisher's exact test and Pearson's chi-square test were applied to compare the two groups. The data were analyzed using SPSS version 23. A P-value < .05 was considered significant. Results A total of 93 cases of Brucella bacteremia were enrolled, with 64 (68.8%) patients being male, and the group mean age being 44.3 ± 19.2 years. Overall, 37 (39.8%) patients received IV regimen, while 56 (60.2%) received oral treatment. Follow-up blood culture negativity after four weeks for both groups was 90.3% (n=84) with no difference between the oral and IV regimens (87.5% (n=49) versus 94.6% (n=37); P= .348, respectively). The overall clinical cure rate was 93.5% (n=87) for both groups combined, with no significant difference between the oral and IV groups (91% (n=51) versus 97.3% (n=36); P= .397, respectively). Transaminitis (7.1% vs. 5.4%), vomiting (5.4% vs. 8.1%), and acute kidney injury (0% vs. 2.7%) were all reported in the oral and IV groups, respectively, with no statistically significant difference between the two groups (P =.590). No deaths were reported over this period. Conclusion Oral and IV antimicrobial regimens have the same response rates in Brucella bacteremia patients. Disclosures All Authors: No reported disclosures.