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The present study compares the efficacy and safety of sequential i.v. cefuroxime (CFX)/oral CFX-axetil versus i.v. sulbactam-ampicillin (SAM)/oral amoxicillin-clavulanate (AC) therapies in hospitalized male soldiers with moderate community-acquired pneumonia (CAP). A total of 72 patients were randomized to receive either CFX 750 mg administered i.v. tid or SAM 1000 mg administered i.v. bid, all for three days. Although WBC counting, CRP measurement and chest X-ray were performed before and three days after the therapy, only clinical response on the third day was taken into consideration to switch to oral therapy. If clinical improvement was seen with i.v. treatments, therapy continued with oral CFX-axetil 500 mg bid after i.v. CFX (CFX-CFX group) and with oral AC 625 mg tid after i.v. SAM (SAM-AC group). Among 72 patients, 67 were evaluable. WBC counts and radiographic infiltrations at switch time to oral therapy showed a statistically significant decrease that was consistent with clinical response (p<0.05), but CRP levels (p>0.05). Clinical success (cure or improvement) was obtained in 28 (90%) and 34 (94%) patients from CFX-CFX and SAM-AC groups, respectively (p>0.05), and maintained in the follow-up period. Both regimens were well tolerated except gastrointestinal side effects, which were observed in two patients from CFX-CFX group (3.2%) and three patients from SAM-AC group (5.5%). In conclusion, both sequential therapy modalities are of similar efficacy and safety in the treatment of moderate CAP. Clinical assessment is essential to decide when to change to oral therapy, but WBC counting and chest radiograph can also be helpful.