This prospective within-group multicentre study was designed to assess the safety and short-term effectiveness of manual lung hyperinflation in mechanically ventilated patients. Eighteen patients from the intensive care units of two tertiary institutions were included and acted as their own control. Manual lung hyperinflation treatment involved patient positioning (side-lying), suctioning and manual lung hyperinflation. Side-lying treatment involved patient positioning and suctioning alone. Patients received both treatments on the day of data collection. Results demonstrated significant improvement for static respiratory system compliance (P = 0.001) with manual lung hyperinflation treatment compared to side-lying treatment. Manual lung hyperinflation treatment also cleared a significantly greater wet weight of sputum (P = 0.039). There were no differences between manual lung hyperinflation and side-lying treatment for gas exchange (PaO2/FIO2 and PaCO2), mean arterial pressure or heart rate. In conclusion, total static respiratory system compliance and sputum clearance were improved by the addition of manual hyperinflation to a physiotherapy treatment of positioning and suctioning in mechanically ventilated patients without compromise to cardiovascular stability or gas exchange.