OBJECTIVES: To carry out a systematic review of the literature comparing the cost-effectiveness of thrombolytic agents currently available in the UK for treatment of AMI in either a hospital or pre-hospital setting. The aim of this review was to identify economic evaluations that had been undertaken in the context of high quality randomised controlled trials in order to inform UK NHS decision-making. METHODS: The search included a number of strategies. Search terms for electronic databases (MEDLINE, EMBASE, HTA, DARE, NHS-EED, Cochrane Trials Register) included a combination of index terms and free word text. Using explicit, predetermined criteria, two reviewers independently identified studies for inclusion in the cost-effectiveness review process. Quality assessment using the Drummond 10-point checklist was also performed. RESULTS: No studies in the pre-hospital setting met the inclusion criteria. In the hospital setting, 107 papers were considered for inclusion in the review and 8 met the inclusion criteria. All of the studies justified their choice of comparator, performed incremental cost-effectiveness analysis and included relevant comparators. Authors in Europe applied the results of the GUSTO I study to their own settings in an attempt to compare the cost-effectiveness of alteplase versus streptokinase. Consequently, cost-effectiveness ratios were expressed in several currencies, a reflection of the international interest in the choice between alteplase and streptokinase. Some studies did not sufficiently explore the true cost of complications over the patient's lifetime, nor was this addressed fully by sensitivity analysis. Only three studies considered issues that can be addressed by cost-utility analyses. Overall the studies were of good quality. CONCLUSIONS: Existing economic evaluations are of limited value in determining the relative cost-effectiveness of thrombolytic drugs in the NHS. Published studies are almost all industry funded and interpretation of results depends on whether one accepts or rejects the assumption of superiority of alteplase over streptokinase.