Background In experimental and clinical studies, volatile anaesthesia has proven to possess cardioprotective properties. However, no randomized controlled trials on the use of isoflurane during the entire cardiac surgical procedure are available. We therefore compared isoflurane–sufentanil vs propofol–sufentanil anaesthesia in patients undergoing coronary artery bypass grafting. Methods One hundred patients were randomly assigned to receive isoflurane–sufentanil (I) ( n = 51) or propofol–sufentanil (P) ( n = 49) anaesthesia, aimed at the same hypnotic depth. Postoperative concentrations of cardiac troponin I (cTnI) were followed for 72 h. Secondary outcome variables were length of stay (LOS) in the intensive care unit (ICU) and in hospital, and 30 day and 1 yr mortality and morbidity, defined as acute myocardial infarction, arrhythmias, and cardiac dysfunction. Groups were compared by an on-treatment analysis, using linear mixed models for repeated measures. Results Eighty-four patients completed the protocol (I: 41 vs P: 43). Postoperative cTnI concentrations increased to a maximum of I: 2.72 ng ml −1 (1.78–5.85) and P: 2.64 ng ml −1 (1.67–4.83), but did not differ between groups ( P =0.11). LOS in the ICU and in hospital was similar [ICU I: 18 (17.0–21.5) vs P: 19 (17.0–22.0) h; hospital I: 9 (6.5–8.0) vs P: 8 (6.0–9.0) days]. Cardiac morbidity and mortality in hospital and 30 days after surgery did not differ between groups. One year after surgery, two patients had died of non-cardiac causes. No between-group differences in cardiac morbidity were found. Conclusions In this study, the use of isoflurane–sufentanil in comparison with propofol–sufentanil anaesthesia does not afford additional reduction of postoperative cTnI levels. Clinical trial registration information: NCT00356746 (http://www.clinicaltrials.gov/ct2/show/NCT00356746?term=NCT00356746&rank=1).