The primary aim of this study was to evaluate the pain relief and tolerability of two pain-relieving strategies in the prehospital phase of presumed acute coronary syndrome (ACS), and the secondary aim was to assess the relationship between the intensity and relief of pain and heart rate, blood pressure, and ST deviation. Patients with chest pain judged as caused by ACS were randomized (open) to either metoprolol 5 mg intravenously (i.v.) three times at 2-min intervals (n = 84; metoprolol group) or morphine 5 mg i.v. followed by metoprolol 5 mg three times i.v (n = 80; morphine group). Pain was assessed on a 10-grade scale before randomization and 10, 20, and 30 min thereafter. The mean pain score decreased from 6.5 at randomization to 2.8 30 min later, with no significant difference between groups. The percentages with complete pain relief (pain score <=1) after 10, 20, and 30 min were 11, 16, and 21%, respectively, with no difference between groups. Hypotension was less frequent in the metoprolol group compared with the morphine group (0 vs. 6.3%; P=0.03), as was nausea/vomiting (7.2 vs. 24.0%; P=0.004). At randomization intensity of pain was associated with degree of ST elevation (P=0.009). The degree of pain relief over 30 min was associated with decrease in heart rate (P=0.03) and decrease in ST elevation (P=0.01). In conclusion, in the prehospital phase of presumed ACS, neither a pain-relieving strategy including an anti-ischemic agent alone nor an analgesic plus anti-ischemic strategy in combination resulted in complete pain relief. Fewer side effects were found with the former strategy. Other pain-relieving strategies need to be evaluated.