The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective neutering of seven healthy cats, premedicated intramuscularly with 0.3 mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood samples were collected over 240 minutes, and propofol concentrations were measured via a validated high-performance liquid chromatography assay. Selected pharmacokinetic parameters, determined by a three-compartment open linear model, were entered into a computer-controlled infusion pump (target-controlled infusion-1 (TCI-1)). In a second step, TCI-1 was used to induce and maintain general anaesthesia in nine cats undergoing neutering. Predicted and measured plasma concentrations of propofol were compared at specific time points. In a third step, the pharmacokinetic parameters were modified according to the results from the use of TCI-1 and were evaluated again in six cats. For this TCI-2 group, the median values of median performance error and median absolute performance error were −1.85 per cent and 29.67 per cent, respectively, indicating that it performed adequately. Neither hypotension nor respiratory depression was observed during TCI-1 and TCI-2. Mean anaesthesia time and time to extubation in the TCI-2 group were 73.90 (±20.29) and 8.04 (±5.46) minutes, respectively.