Parapneumonic effusion or pleural empyema (PPE/PE) is a frequent complication of community-acquired pneumonia (CAP) in children. Different management approaches exist for this condition. We evaluated a 14-day treatment with amoxicillin (AMX) with/without clavulanic acid (AMC) confirmed or modified by microbiological findings from pleural tap. Children ≤16 years of age with radiologically diagnosed PPE/PE and initial diagnostic pleural tap were included at University Children's Hospital Zurich from 2001-2015. AMX/AMC was given for 14 days and rationalized according to microbiological pleural tap results. Clinical and radiological follow-up was scheduled until six months or full recovery. In 114 of 147 (78%) children with PPE/PE a pathogen was identified by culture, polymerase chain reaction (PCR), and/or antigen testing. was detected in 90 (79%), in 13 (11%), and in seven cases (6%), all but two cultured pathogens (96%) were sensitive to AMX/AMC. One-hundred two of 147 (69%) patients received treatment with AMX/AMC for 14 days. They recovered more rapidly than patients with a different management ( = 0.026). Of 139 children with follow-up, 134 (96%) patients fully recovered. In conclusion, 14-day AMX/AMC treatment confirmed and rarely modified by microbiological findings from pleural tap resulted in full recovery in >95% of children with PPE/PE.