Background and Objectives: Septoplasty is one of the most common surgical procedures in specialty of otorhinolaryngology. Therefore, there are frequent thoughts regarding this procedure to improve its conditions from different aspects, indications, time of surgery, techniques, safety measures, and postoperative care. One of big issues regarding this procedure is the post-operative sequel and complications namely post-operative pain, oro-facial edema, air way obstruction, epistaxis, nausea and vomiting, nasal obstruction, atrophic rhinitis, induction of allergic rhinitis, septal perforation and synachia formation. Therefore, this study was conducted prospectively to confirm the effect of intravenous administration of dexamethasone on outcomes of this procedure as compared to the effect of oral administration of ketoprofen as well as paracetamol after septoplasty procedure. Patients and Methods: Two- thousands and two- hundred thirteen patients aged from 4 years to 65 years presented at ENT department-Althowra central teaching hospital as well as Altarahom private clinic-elbyda city-Libya at period in between September 2005 to January 2022 as cases of DNS with variable patterns of septal deformities for septoplasty. Five hundred thirty- one patients were received oral paracetamol who represent group-A, 753 received oral ketoprofen that constitutes group-B, while remaining 929 were administrated by intravenous dexamethasone and classified as group-C. As prospective analytic study, three groups compared in relation to significant postoperative complications risk namely post-operative pain, oro-facial edema, airway obstruction, epistaxis, nausea and vomiting, nasal obstruction, atrophic rhinitis, induction of allergic rhinitis, septal perforation and synachia formation. In addition, these groups compared for any significant difference regarding the period of postoperative hospitalization, which can be used, as objective indicator to measure the postoperative morbidity rate. Results: Dexamethasone as well as ketoprofen administration caused significant improvement in pain intensity as compared to paracetamol group. On the other hand there was significant reduction in the incidence of post-operative oro-facial edema, air way obstruction, epistaxis, nausea and vomiting, nasal obstruction, atrophic rhinitis, induction of allergic rhinitis, septal perforation and synachia formation among group-B and C as compared to group-A. Conclusion: Dexamethasone can be considered as potent analgesic drug after septoplasty procedure and in same time, it plays significant role in the improvement of outcomes of this common procedure as compared to the other commonly used non-steroidal anti-inflammatory drugs.