After cardiac surgery, patients often require prolonged mechanical ventilation. We studied the effectiveness and potential toxicity of isoflurane sedation in 40 patients undergoing mechanical ventilation after cardiovascular surgery. All patients who received isoflurane (0.5-1.0 minimum alveolar concentration [MAC] were well sedated by it without significant adverse effects, such as renal, hepatic, or cardiovascular dysfunction. The highest serum inorganic fluoride concentration recorded was 45 mumol/L after 98 MAC h. Patients on isoflurane recovered more rapidly and were weaned from mechanical ventilation sooner than those sedated with intravenous drugs including fentanyl/midazolam. Patients who received intravenous sedatives, but not those on isoflurane, often showed tachyphylaxis in the early stages, and some exhibited an abstinence syndrome involving nonpurposeful movements. Patients sedated with isoflurane did not show these two side effects. In conclusion, isoflurane can provide effective long-term sedation for patients after cardiovascular surgery without significant adverse effects.