This multicentre, non-comparative study investigated the range of target blood propofol concentrations required to sedate 122 adult intensive care patients when propofol was administered using Diprifusor™ target-controlled infusion systems together with opioid analgesia. Depth of sedation was assessed with a modified Ramsay score and the target blood propofol setting was adjusted to achieve the sedation desired for each patient. A desired level of sedation was achieved for 84% of the sedation period. In postcardiac surgery patients the median time-weighted average propofol target setting was 1.34 μg.ml−1 (10th – 90th percentiles: 0.79–1.93 μg.ml−1). Values in brain injured and general ICU patients were 0.98 (10th – 90th percentiles: 0.60–2.55) μg.ml−1 and 0.42 (10th – 90th percentiles: 0.16–1.19) μg.ml−1, respectively. Measured propofol concentrations were generally close to values predicted by the Diprifusor™ system. Target settings in the range of 0.2–2.0 μg.ml−1 are proposed for propofol sedation in this setting with titration as required in individual patients.