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Abstract Background Large thrombus burdens in ectatic coronary arteries that remain after aspiration thrombectomy can negatively impact outcomes following percutaneous coronary interventions in patients with acute myocardial infarction. Case presentation A 53-year-old man presented with ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed an ectatic right coronary artery (RCA) that was completely occluded in the mid portion by a large amount of thrombus. Catheter-directed intracoronary thrombolysis with alteplase led to recovery of coronary blood flow, which multiple attempts of aspiration thrombectomy had failed to achieve. Coronary angiography 9 days later showed good blood flow and insignificant stenosis remaining in the RCA; this had completely resolved in 6 months’ follow-up coronary angiography. Conclusion Catheter-directed intracoronary thrombolysis can be performed effectively and safely when repeat aspiration thrombectomy fails to produce satisfactory coronary reperfusion in STEMI patients with large thrombus burdens in ectatic coronary arteries.