Background: In patients with ST-elevation myocardial infarction (STEMI), C-reactive protein (CRP) levels are associated with larger infarct size, transmural extent, and poor function of left ventricle and independently predict 30-day mortality. CRP-apheresis following STEMI showed to be feasible, safe, and has significant beneficial effect both on myocardial infarction size and wall motion. To the best of our knowledge, this is only the second published clinical evaluation of the efficacy and safety of selective CRP-apheresis in the STEMI treatment using Spectra-Optia and Pentrasorb CRP-adsorber systems. Case Report: A 53-year-old female was referred with anterior STEMI. After percutaneous coronary intervention, patient received standard post-STEMI therapy according to current guidelines. Selective therapeutic plasma exchange (TPE) was performed using Spectra-Optia (Terumo BCT; USA) and Pentrasorb CRP-adsorber (Pentracor GmbH; Germany) systems. Antecubital veins were used for vascular access and acid-citrate-dextrose solution (ACD formula A; total volume = 1,026 mL) was utilized as anticoagulant. The volume of processed blood was 15,600 mL. The removed “natural” plasma (total volume = 8,329 mL) was replaced with CRP-depleted autologous plasma (total volume = 8,085 mL). This intensive TPE-treatment was well tolerated, without adverse effects, or complications. The CRP plasma levels were: initial = 4.2 mg/L 6 h after acute myocardial infarction (AMI), pre-apheresis = 16.4 mg/L, and post-apheresis = 4.59 mg/L (CRP-depletion = 72%). There were neither significant changes observed in biochemistry nor any alterations in plasma hemostatic activity investigated before and after CRP-adsorption performed. Conclusion: Early performed CRP-apheresis is a promising innovative therapeutic approach for STEMI treatment that could provide a reduced size of infarction zone – with inferior occurrence of heart failure after AMI. However, precise and complete evaluation of the efficacy and safety of this treatment requires further multicenter randomized and larger clinical studies.