Introduction Vaccine hesitancy is a complex public health issue referring to concerns about the safety, efficacy or need for vaccination. Relatively little is known about vaccine hesitancy in Switzerland. This ongoing study (2017–2021) focuses on biomedical and complementary and alternative medicine (CAM) providers and their patients since healthcare professionals play important roles in vaccination decision-making. This national research programme seeks to assess the sociocultural determinants of vaccine hesitancy regarding childhood and human papillomavirus vaccines in Switzerland. We aim to provide a detailed characterisation of vaccine hesitancy, including CAM and biomedical perspectives, patient–provider interactions, and sociocultural factors, to establish the mediating effects of vaccine hesitancy on underimmunisation, and to design an intervention to improve vaccination communication and counselling among physicians, parents and adolescents. Methods and analysis Our transdisciplinary team employs a sequential exploratory mixed-methods study design. We have established a network of more than 150 medical providers across Switzerland, including more than 40 CAM practitioners. For the qualitative component, we conduct interviews with parents, youth, and biomedical and CAM providers and observations of vaccination consultations and school vaccination information sessions. For the quantitative component, a sample of 1350 parents of young children and 722 young adults (15–26 years) and their medical providers respond to questionnaires. We measure vaccine hesitancy with the Parent Attitudes about Childhood Vaccines 15-item survey and review vaccination certificates to assess vaccination status. We administer additional questions based on findings from qualitative research, addressing communication with medical providers, vaccine information sources and perceptions of risk control vis-à-vis vaccine-preventable diseases. The questionnaires capture sociodemographics, political views, religion and spirituality, and moral foundations. Ethics and dissemination The study was approved by the local ethics committee. The results will be published in peer-reviewed journals and disseminated to healthcare professionals, researchers and the public via conferences and public presentations.