The management of complicated parapneumonic effusions by conventional first-line treatment with closed intercostal tube drainage and antibiotic therapy may fail because of thick viscous fluid and multiple pleural space loculations. Intrapleural fibrinolytic treatment is a non-invasive therapeutic option. In this report, we present successful use of intrapleural streptokinase for complicated parapneumonic effusion and empyema in 2 newborns. Intrapleural fibrinolytic therapy with streptokinase appears to be a safe and effective adjunctive therapy of choice and may have significant benefit even in newborns with complicated parapneumonic effusion and empyema, and thus, it can obviate surgical intervention. (C) 2012 Elsevier Inc. All rights reserved.