The objective of the study was to compare the influence of a fentanyl and droperidol mixture (neuroleptanalgesia) with morphine on the in-hospital instability, development of acute myocardial infarction (AMI), and mortality during a 30-day and 12-month follow-up in unstable angina patients. The study was performed in 112 unstable angina patients. In addition to standard therapy for unstable angina (aspirin, heparin, nitroglycerin, and oxygen), 53 patients (63.2 +/- 9.7 years; 32 males) were randomized to receive neuroleptanalgesia (0.025 mg fentanyl and 1.25 mg droperidol in a volume of 1 mL) and 59 patients (58.6 +/- 11.5 years; 41 males) to receive morphine. Neuroleptanalgesia was started i.v. with 2 mL and could be followed by 1 mL every 4 hours. Morphine was started i.v. with 10 mg and could be followed by 5 mg every 4 hours up to angina resolution during 24 hours of hospitalization. Another 1 mL of neuroleptanalgesia or 5 mg of morphine could be administered on demand if angina lasted or reappeared earlier than the next scheduled dose. Odds ratios with 95% confidence intervals (95% CI) adjusted for the age, sex, smoking, previous myocardial infarction, and hypertension were evaluated for all study outcomes. The odds ratios for clinical in-hospital instability (5.93, 95% CI: 2.49-14.15; P = 0.0001), 12-month AMI development (3.57, 95% CI: 1.51-8.45; P = 0.0038), and 12-month mortality (6.00, 95% CI: 1.63-22.09; P = 0.0070) were significantly increased in the neuroleptanalgesia group compared with the patients on morphine. It is concluded that neuroleptanalgesia negatively influences disease course, AMI development, and total mortality in unstable angina patients.