The diaphragm is the main inspiratory muscle and the main indicator of diaphragmatic contractility is the trans-diaphragmatic pressure (Pdi). The aim of this clinical study was to determine the effect of four different anaesthetic protocols on Pdi in anaesthetized healthy dogs. Eighty client-owned dogs were recruited in this clinical study. All the animals received dexmedetomidine and morphine as premedication and propofol for induction. Anaesthesia was maintained with one of four protocols: isoflurane (I), isoflurane with CRI of propofol (IP), isoflurane with CRI of fentanyl (IF), and isoflurane with CRI of ketamine (IK). When the surgical plane of anaesthesia was achieved, two balloon catheters were inserted, one into the stomach and one into the mid-third of the oesophagus for Pdi measurement. Pdi value was the highest in groups I (14.9±4.7 mmHg) and IK (15.2±3.5 mmHg) and the lowest in groups IP (12.2±3.2 mmHg) and IF (12.0±5.9 mmHg). There was a statistically significant difference (p = 0.029) between groups IK and IF. PE'CO2 was statistically significantly higher (p<0.0005) in group IF (7.7±0.8 kPa) than in group IK (6.5±0.7 kPa). Isoflurane alone or isoflurane with ketamine for the maintenance of anaesthesia seem to better preserve the respiratory function and the diaphragmatic contractility than isoflurane with either propofol or fentanyl in dogs. Therefore, the use of isoflurane or isoflurane with ketamine may be of benefit when animals with respiratory problems have to be anaesthetized.