A hospital-based prospective study of 99 patients with community-acquired pneumonia (CAP) was carried out in Kampala, Uganda. We evaluated microbiological etiologies, clinical features and effectiveness of short-term parenteral ampicillin followed by oral amoxicillin for these patients in relation to HIV-status. We demonstrated a very high prevalence (75%) of HIV-1 infection. No significant difference was observed with respect to age, gender, prior antibiotic usage, symptoms, laboratory data or bacterial etiology between HIV-1-infected and HIV-uninfected CAP patients. Most strains of Streptococcus pneumoniae (n = 19) and Haemophilus influenzae (n = 8) isolated from HIV-1-infected patients were penicillin-resistant (95%) and beta-lactamase producing (75%) strains, respectively. A high percentage of good clinical response was found in both HIV-1-infected (81%) and HIV-uninfected (86%) among 39 patients with CAP due to a defined bacterial pathogen. These data support the use of short-term parenteral ampicillin for patients with bacterial CAP irrespective of HIV-status.