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Objectives: Vaccination is an effective way to reduce morbidity and mortality related to infectious diseases. In France, primary care physicians are the main administrators of vaccines. Our objective was to conduct an exploratory qualitative study with primary care physicians to identify determinants of their commitment to vaccination. Methods: A qualitative research study was conducted with 36 primary care physicians from different geographical regions in France. Six focus group discussions, following a semi-structured interview guide, were held. Qualitative analysis based on coding of the transcribed discussions was performed to identify the factors influencing primary care physicians’ attitudes toward vaccination. These factors were then organized into themes. Saturation was also evaluated. Results: Diphtheria, tetanus, poliomyelitis, measles, mumps, rubella, hepatitis B, tuberculosis, pneumococcal infections, meningococcus, human papillomavirus, rotavirus, pertussis, varicella and flu vaccinations were all discussed in each focus group. Saturation was reached from the fourth focus group. Forty identified determinants were divided into six themes: vaccine characteristics, disease characteristics, primary care physicians’ past experience, practical aspects, expected benefits and primary care physician-patient relationship. Conclusions: This study identified the behavioural and organizational determinants influencing primary care physicians’ attitudes toward vaccination. These attitudes and determinants varied according to diseases and vaccines. The identified determinants and themes were used as a basis for the development of a questionnaire evaluating the Determinant of Vaccination Intentions (DIVA) of primary care physicians.