Volatile anaesthetics differ in the effects they have on splanchnic haemodynamics and oxygenation. The aim of this study was to evaluate the effects of desflurane and isoflurane as part of a balanced anaesthetic technique on intestinal tissue oxygenation during colorectal surgery. Data were analysed from 44 patients randomly assigned to receive either desflurane (desflurane group, n = 20), or isoflurane (isoflurane group, n = 24) for inhalational anaesthesia. Tissue oxygen pressure (P(tiss)O2) was measured on the serosal side of the large intestine prior to colonic resection (T1) and following the completion of the bowel anastomosis (T2). In addition, haemodynamic and oxygenation parameters were assessed. No difference in mean P(tiss)O2 was observed between the groups at T1 [desflurane group: 8.1 (2.9) kPa vs. isoflurane group: 7.7 (2.7) kPa]. Following completion of the anastomosis (T2) mean P(tiss)O2 was higher in the isoflurane group [9.6 (2.9) kPa] than the desflurane group [7.7 (2.4) kPa, p = 0.025]. During surgery no difference between the groups could be observed with regard to haemodynamics and global oxygenation parameters. The lack of a difference between the groups in P(tiss)O2 before resection of the colon suggests that, under normal conditions, desflurane and isoflurane have comparable effects on intestinal blood flow and oxygenation. However, following local ischaemia, the reactive hyperaemia seems to be better preserved during isoflurane anaesthesia indicated by a local increase in P(tiss)O2blank(p = 0.013) following completion of the bowel anastomosis.