Background Left ventricular (LV) remodeling in ischemic cardiomyopathy is the leading cause of heart failure and is an established prognostic factor for adverse cardiovascular events. Experimental studies suggest that sodium tanshinone IIA sulfonate attenuates cardiac remodeling in animal models of acute myocardial infarction (AMI). However, the effects of this drug in the clinical setting remain unclear. Therefore, the STAMP-REMODELING trial is set up to investigate whether treatment with sodium tanshinone IIA sulfonate would prevent the maladaptive progression to adverse LV remodeling in patients following ST-segment elevation myocardial infarction (STEMI). Methods Approximately 80 patients with STEMI successfully treated with primary percutaneous coronary intervention (PCI) will be enrolled and randomized to receive sodium tanshinone IIA sulfonate (80 mg q.d. for 7 days) in addition to standard therapy or the same volume of hydration per day. The primary endpoint is the variation in LVend-diastolic volume index (LVEDVi) assessed with cardiac magnetic resonance imaging (CMR) at baseline and 6 months. Conclusion This study will provide important clinical evidence on the efficacy of sodium tanshinone IIA sulfonate treatment in patients with STEMI when used in combination with current therapies that may significantly reduce adverse LV remodeling and potentially improve clinical outcomes.