Background: Pneumonia is one of the common infection-related death. Recently use of biomarkers in diagnostic and therapeutic approach to pneumonia has been considered. The aim of our study is to evaluate the length of antibiotic treatment, length of hospitalization and medical outcomes in procalcitonin-guided antibiotic therapy in patients with pneumonia. Methods: In a randomized controlled trial study with 134 hospitalized patients with the diagnosis of pneumonia were enrolled to the study and randomly divided into two groups, procalcitonin group (PCT-guided therapy) and control group (customary clinical guidelines). All patients had 14 days follow up. Data were analyzed with appropriate statistical analysis and using version 16 of SPSS statistical software. Results: Totally, the assessed patients were in the range of 18-94 years old and the mean of age in control group was 62.87 ± 19.20 years and mean age of PCT group was 58.34 ± 19.32 years. Length of antibiotic treatment in the PCT group was 3.17 days’ vs 11.38 days in the control group (P < 0.0001). Length of hospitalization in the PCT group was 4.53 days’ vs 6.75 days in the control group that was significantly reduced (P < 0.0001). In 14 days follow up all patients had not any complication and clinically improved. Conclusions: In conclusion, procalcitonin-guided antibiotic treatment in patients with acute respiratory infections effectively reduced antibiotic exposure and antibiotic side-effects while reducing the length of hospitalization and treatment duration and accordingly, decrease the expenditure of patients’ treatment and avoid antibiotic resistance.