Objectives Therapeutic patient education improves numerous health and psychological outcomes in patients with chronic diseases. However, little is known about what makes a therapeutic patient education intervention more effective than another one. This study aims to identify in healthcare professionals the perceived determinants of therapeutic patient education efficacy at the individual level. Methods Semi-structured individual interviews have been conducted with healthcare professionals (HCP, n=28, including 20 nurses) involved in therapeutic patient education programs ( n=14) covering various chronic conditions (kidney and cardiovascular diseases, chronic pain, diabetes, etc.). A thematic content analysis following an inductive approach was used (Nvivo.11 software). Results Five themes were retrieved for patient characteristics: understanding and education, personality, readiness and motivation, social environment, and misinformation and beliefs. Four themes were retrieved for healthcare professionals’ characteristics: medical knowledge, appropriate attitude and relational skills, pedagogical skills, and training. Discussion Patient personality is rarely discussed in the literature. Patients who are introverted, lack curiosity, or are not compliant might benefit from specific therapeutic patient education practices or formats. All these potential determinants regarding patients and healthcare professionals should be routinely assessed in future studies about therapeutic patient education efficacy to understand precisely what makes an intervention successful.