This paper identifies challenges for conducting Decentralized Clinical Trials (DCTs) in Denmark from key stakeholders’ perspectives. Challenges concern defining and disseminating DCT activities and implementing recruitment strategies. For remote access to source data and validating endpoints, challenges include quality assurance and data transfer. Challenges for IT systems include data capture, transfer, harmonization, and backup. Challenges are concerned with over/under-reporting when reporting side effects. Documentation and safety challenges occur for Investigational Medical Product (IMP) shipment and home administration. Concerning the surveillance of trial participants’ (TP) safety, the principal investigator’s (PI) oversight is the main challenge. National working groups are established for selected areas of DCTs.