Objective: To compare the efficacy of sequential injectable crystalline penicillin (C.pen) and gentamicin combination followed by amoxicillin with sequential IV and oral amoxicillin-clavulanate (amox-clav) in treatment of severe or very severe hypoxemic pneumonia.Methods: Children aged 2–59 months with WHO-defined severe or very severe pneumonia with hypoxemia (SpO2<90%) were included in the study. Patients with fever>10 days, bacterial meningitis, prior antibiotic therapy >24 hours, stridor, heart disease and allergy to any of the study drugs were excluded. They were randomly allocated to two groups—Group A and Group B. Group A received C. pen and gentamicin intravenously (IV), followed by oral amoxicillin and group B got amox-clav IV, followed by oral amox-clav. Minimum duration of IV therapy was 3 days and total 7 days. Respiratory rate, oxygen saturation and chest wall indrawing were monitored 6 hourly.Results: 71 patients were included. There were two (5.2%) blood cultures positive in group A and three (9%) in group B. Organisms isolated wereS. pneumoniae (n=3) andH. influenzae-b (n=2). There was only one treatment failure in each of the groups. One was due to penicillin resistantH. influenzae-b and the other was due to worsening of pneumonia. The mean time taken for normalization of tachypnea, hypoxia, chest wall indrawing and inability to feed was similar (P-N.S). Mean duration of IV therapy in group A was 76±25 hrs and group B was 75±24 hrs (p>0.1).Conclusion: In children of 2–59 months, sequential injectable C. pen and gentamicin combination, followed by oral amoxicillin or sequential IV and oral amox-clav were equally effective for the treatment of severe or very severe hypoxemic community acquired pneumonia.