The informed consent (IC) of subjects participating in experimental studies is the mainstay to comply with the ethical principle of autonomy to ensure that the participation is voluntary. This experience was performed within the context of a single-center randomized clinical trial in elective prosthetic surgery. Obtaining IC in clinical trials is not without difficulties, and especially in the case of vulnerable populations it can be very challenging. This work aimed to identify the difficulties during the IC process for a clinical trial in subjects older than 65 years old and quantify and describe the use of IC in front of a witness. Methods: This is a mixed methodology study with a qualitative part (focus group with 4 nurses involved in the inclusion of subjects) and a quantitative part describing the characteristics of patients who signed IC forms. Results: The main difficulties identified are related to comprehension, sensory impairments, education level, and time. IC in front of witnesses was used in 20 patients out of 508. Conclusions: The participation of subjects older than 65 years old in clinical trials requires an adaptation of the process. The use of IC in front of a witness should always be considered in studies including elderly subjects.