The improper use of antibiotics has led to increased emergence of resistant organisms, making it essential to investigate Healthcare providers’ perceived barriers to effective administration of prescribed antibiotics to inpatients in National Orthopaedic Hospital Enugu (NOHE) Nigeria. Study adopted a descriptive cross sectional design. The target population was 344 doctors and nurses, 273 met the inclusion criteria and were involved in the study. Data were collected using questionnaire, items constructed in 4 point Likert type response scale with decision mean score of 2.5. Data were analyzed with the aid of statistical package for social science (SPSS) version 20. The result showed financial constraint as the major patients’ barrier (3.4), improper timing as the major healthcare providers’ barrier (3.0) and lack of antibiotics stewardship as the major health system barrier (3.2). There was no significant relationship (p>0.05) between the professional status, gender and years of experience of the healthcare providers and their perceived barriers to effective antibiotics administration. Patients should be educated on antibiotics use, and encouraged to register with Health Insurance Scheme which is designed to alleviate the financial burden associated with healthcare services. Healthcare providers should administer antibiotics as prescribed and hospital system has to set-up antibiotics stewardship.