Introduction: Copper-64 is an attractive radionuclide for positron emission tomography and is emerging as a radiotherapeutic agent. The demand of Cu-64 with low metallic impurities has increased because of its wide applications when incorporated with antibodies, peptides, and proteins. In this study, we propose a new separation method to produce high-quality Cu-64 using a cation exchange column, as well as an automated separation system suitable for large-scale production. Methods: Cu-64 was produced from an electrodeposited Ni-64 target via the Ni-64( p,n)-reaction with a 24 MeV HH + beam at 10 epA (electrical microampere) conducted for 1-3 h. The irradiated target was transported to a hot cell and disassembled remotely. (64)Cuwas separated by a solvent mixture of HCl and acetone on a cation-exchange resin, AG5OW-X8. The chemical purity of 64Cu final product was evaluated using ion-chromatography coupled with a UV detector and inductively coupled plasma mass spectroscopy for quality as well as metallic impurities. Results: We obtained Cu-64 in dried form at a yield of 52-13 GBq at the end of separation, or 521 +/- 12 MBq/epA h as the final product within 2.5 h of processing time. The metallic impurities were a satisfactory low level in the order of ppb. Major contaminants of Co and Ni were lower than those samples obtained by a widely accepted separation using an anion-exchange resin. Conclusion: Using a cation-exchange resin and a systematic operation, we successfully reduced the contamination level of the Cu-64 product. As a straightforward separation method, which shortened the entire processing time, we obtained a satisfactory amount of high-quality Cu-64 available for routine use. (C) 2016 Elsevier Inc. All rights reserved.