Aim: This research aimed to study the association of drug interactions and sociodemographic, clinical, and functional characteristics in nonagenarians with hyperpolypharmacy. Methods: This was a secondary analysis of an evaluation performed by the Multiprofessional Care for the Oldest-old Project in 2016, with participants identified with hyperpolypharmacy. Results: Results revealed that 69% of 29 participants had at least one major drug interaction, 41% had 10 or more moderate interactions, and 59% had minor interactions. The study revealed significant relationships for major drug interactions with the characteristics of recurrent urinary tract infections, anxiety, and palpitations. The study found near significance for white color, not good general health and appetite, depression, and impaired cognition. For moderate drug interaction, findings showed a relationship near significance for females, perception of not good general health and appetite, hypertension, diabetes, urinary infection, depression scale change, agitation, pain, fatigue, and a fear of falling. For minor drug interactions, the study revealed significant findings for an association with depression, and apathy or sleepiness. There were findings near significance for an association with white color, diabetes, agitation, pain, fatigue, and cough. Conclusion: Drug interactions are highly prevalent among nonagenarians with hyperpolypharmacy, with clinical and quality of life impact. Thus they must be constantly evaluated for the presence of drug interactions at all levels of care, whether in primary care or in specialized care. A study with larger sample size and longitudinal contour is proposed to prove the importance of our observations.