OBJECTIVE: The objective of this study is to measure the impact of a five-step implementation process for an acute myocardial infarction (AMI) clinical pathway (CPW) on thrombolytic administration in rural emergency departments. DESIGN: Cluster randomised controlled trial. SETTING: Six rural Victorian emergency departments participated. INTERVENTION: The five-step CPW implementation process comprised (i) engaging clinicians; (ii) CPW development; (iii) reminders; (iv) education; and (v) audit and feedback. MAIN OUTCOME MEASURES: The impact of the intervention was assessed by measuring the proportion of eligible AMI patients receiving a thrombolytic and time to thrombolysis and electrocardiogram. RESULTS: Nine hundred and fifteen medical records were audited, producing a final sample of 108 patients eligible for thrombolysis. There was no significant difference between intervention and control groups for median door-to-needle time (29 mins versus 29 mins; P = 0.632), proportion of those eligible receiving a thrombolytic (78% versus 84%; P = 0.739), median time to electrocardiogram (7 mins versus 6 mins; P = 0.669) and other outcome measures. Results showed superior outcome measures than other published studies. CONCLUSIONS: The lack of impact of the implementation process for a chest pain CPW on thrombolytic delivery or time to electrocardiogram in these rural hospitals can be explained by a ceiling effect in outcome measures but was also compromised by the small sample. Results suggest that quality of AMI treatment in rural emergency departments (EDs) is high and does not contribute to the worse mortality rate reported for AMIs in rural areas.