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Introduction: Ceftriaxone is a third generation cephalosporin recommended as first line treatment option for a number of diseases in Uganda. However, the National Drug Authority has in the recent past received complaints of suspected treatment failure from clinicians who use different brands of ceftriaxone in Uganda. The main aim of the study was to document the treatment outcome following use of ceftriaxone and evaluating the use of ceftriaxone against the current treatment guidelines in Uganda. Methods: A descriptive observational, non-intervention study design to document treatment outcomes after administration of Ceftriaxone injection in hospitalized patients was undertaken in Mubende. A total of 100 hospitalized patients treated with ceftriaxone were enrolled. Results: Overall, Ceftriaxone was used to treat pneumonia in the paediatric ward, presumptive therapy for infection following caesarean section (n=47) and PID in the post-natal ward, while on surgical and medical wards, Ceftriaxone was used to manage upper respiratory infection, bacterial infections and meningitis. There were no Adverse Events reported to have occurred during treatment with ceftriaxone. Of the patients treated with ceftriaxone 18% completed their doses and had regular administration. Majority 60% of the patients had irregular administration with completed doses and 22% did not complete their doses. Conclusion: There is low treatment outcome during use of Ceftriaxone and the empirically treatment is highly prevalent in the hospital. There is high number of inappropriate drug administration, in which patients usually miss doses or do not complete as prescribed. This practice has an effect of affecting the patient outcomes and aggravating antimicrobial resistance. Choice of ceftriaxone use is not guided by culture and sensitivity due to lack of inadequate laboratory infrastructure.