Coughing both protects the airways from foreign material and clears excessive secretions in respiratory diseases, and therefore requires high expiratory flows. We hypothesised that the volume inspired prior to coughing (operating volume) would significantly influence the mechanical changes during coughing and thus cough flow. Sixteen healthy volunteers (6 female, mean age 31 ± 10 years) performed six single voluntary coughs from four different operating volumes (10%, 30%, 60% and 90% of vital capacity) followed by three peals of voluntary and citric acid-induced coughs. During coughing we simultaneously measured (i) chest and upper abdominal wall motion using opto-electronic plethysmography (OEP), (ii) intra-thoracic and intra-abdominal pressures with a balloon catheter in each compartment and (iii) flow at the mouth. Operating volume was the most important determinant of the peak flow achieved and volume expelled during coughing, but had little influence on the pressures generated. The duration of single coughs increased with operating volume, whereas coughs were much shorter and varied little during peals. Voluntary cough peals were also associated with significant blood shift away from the trunk. In conclusion, this study has shown that operating volume is the most important determinant of cough peak flow and volume expelled in healthy individuals. During peals of coughs, similar mechanical effects were achieved more rapidly, suggesting a modification of the motor pattern with improved efficiency. Future studies investigating cough mechanics in health and disease should control for the influence of operating volume.