Abstract Background One of the greatest and most effective strategies to decrease the likelihood of discovering antibiotic-resistant bacteria in patients receiving critical care is to shorten the duration of antibiotic therapy. Objectives To assess the utility of procalcitonin compared to traditional inflammation markers like C-reactive protein in an antimicrobial stoppage in patients with septic shock. Methods This was a comparative, prospective, randomized, observer-blind clinical experiment conducted on 60 septic patients hospitalized in intensive care units at Benha University hospitals between May 2021 and May 2022. Groups for PCT and CRP patients were separated. The full clinical history, co-morbidities that were related, and patient history were recorded. The baseline PCT and CRP values were determined on days 4, 7, 10, and 14. They were contrasted with sepsis ratings obtained from the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sepsis-related Organ Failure Assessment (SOFA). Days 4, 7, and 10 were used to evaluate the antibiotic's efficacy. Results There was no correlation between CRP levels and APACHE II and SOFA scores on days 1, 4, and 7, but on days 7 and 10, PCT levels were strongly linked with both (P < 0.05). PCT was linked to lower antibacterial exposure (23.3% of PCT participants ceased taking antibiotics on day 4, compared to 6.6% of CRP participants; P = 0.07). After 10 days, 30% of the PCT group and 70% of the CRP group kept up their antimicrobial regimen (P = 0.0001). Conclusion Procalcitonin dramatically reduced the duration of antimicrobial treatment. Procalcitonin use has reduced hospital expenses, complications of extended hospital stay, side effects of excessive antibiotic use, and hence, the mortality rate in septic patients.