Pleural infection is a common clinical condition leading to hospitalisation. In the last decade, advances in pleural research have led to a paradigm shift in the treatment of complex effusion from a surgical approach to a less invasive non-surgical approach using a combination of intrapleural fibrinolytics and pulmozyme (DNase). We report 3 patients with pleural infection. Intercostal chest catheter failed to drain the complex effusion. They were subsequently treated with a modified short-course regimen of alteplase and DNase. They received 3 cycles of 16 mg alteplase with 5 mg DNase each within 24 hours and all three had a favourable outcome with no adverse effects. This modified regimen appears effective with good safety profile and adds to the current literature on the safety and effectiveness of different dose combinations of alteplase and DNase.