Introduction: Since the 2009 influenza A(H1N1) pandemic, vaccine hesitancy has been widely discussed both nationally and internationally. It is necessary to monitor, at regular intervals, the public’s uptake of vaccination and hesitancy toward certain vaccines. Methods: The 2016 Health Barometer is a random telephone survey conducted between January and August 2016 among 15,216 individuals aged 15 to 75 residing in metropolitan France. The results presented in this article pertain to the 14,875 individuals aged 18 to 75. Results: In 2016, 75.1% of respondents stated that they were in favor of vaccination in general. Support increased significantly compared to 2010 (61.2%) but decreased compared to 2014 (78.8%). Vaccination against seasonal influenza received the highest level of opposition in 2016 (15.4%), followed by vaccination against hepatitis B (13.0%) and vaccination against human papillomavirus (HPV) infections (5.8%). Vaccines for infants elicit little reluctance. The profile of people opposed to vaccination varies depending on the type of vaccine. Reluctance toward seasonal flu vaccination is more prevalent among those aged 25–44, but less so among those with higher levels of education. The profiles of those opposed to hepatitis B and HPV vaccinations are very similar: they are primarily people with high incomes and educational levels, those aged 45–54, and women. Conclusion: The results of this survey show that vaccination uptake is a complex phenomenon involving several sociodemographic factors that must be taken into account to overcome reluctance and restore confidence in vaccination.