People with profound intellectual disabilities often receive medication through enteral feeding tube (EFT). In a previous study, we found that current guidelines concerning medication preparation and administration through EFT are often not followed in residential care facilities (RCFs) for individuals with intellectual disabilities. The present qualitative study aimed to identify barriers and facilitators experienced by RCF staff members to following guidelines on medication administration via EFT, by conducting focus group interviews. Time constraints, lack of knowledge, lack of clear administration instructions, lack of necessary materials, and limited gastric fluid tolerance in certain residents were identified as barriers to following guidelines. Other influencing factors were the number of staff members, residents, and medications; habits; and the residents' comfort and well-being. To optimize care for this vulnerable patient population with EFT, an intervention can be set up focusing on improving staff members' medication-related knowledge and providing clear administration instructions and the necessary materials.