Objectives: To study motor evoked potentials (MEPs) to multi-pulse transcranial electrical stimulation (MP-TES) during orthopaedic spinal surgery under different anaesthetic regimens. Methods: MEPs to MP-TES were recorded from tibialis anterior and abductor hallucis bilaterally in 50 operations. Anaesthesia was maintained with propofol and nitrous oxide in 29 operations and isoflurane (0.78±0.17% end-tidal) and nitrous oxide in 23 (two patients received both regimens). Analgesia was provided with fentanyl or remifentanil. Results: Motor stimulation caused neither EEG changes nor seizures. MEPs were obtained in 97% of patients during propofol anaesthesia. The median amplitude and coefficient of variation (CV) at baseline (across all muscles) were 198 μV and 22%, respectively. Amplitudes throughout the operation paralleled the degree of neuromuscular block and were reduced after fentanyl bolus, isoflurane or morphine. Loss of MEPs or persistent amplitude decrements were associated with neurological complications in one patient and severe blood loss in another two patients. MEPs were obtainable in 61% of patients during isoflurane anaesthesia and became inconsistent for end-tidal concentrations >0.87±0.08%. Amplitudes were smaller (85 μV) and baseline variability higher (coefficient of variation 29%) than in the propofol group. The decrease in the number of recordings was greater for isoflurane than propofol when the number of pulses/train decreased from 4 to 2. Conclusions: Muscle MEPs to MP-TES are a safe, sensitive and reliable method for monitoring motor pathways during propofol/nitrous oxide and fentanyl or remifentanil anaesthesia. MEPs are also obtainable in the majority of patients during isoflurane/nitrous oxide anaesthesia, but quantitative monitoring is not always possible with this regimen.