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Description: Background Monitoring the reasons why a considerable number of people do not receive recommended vaccinations allows identification of important trends over time, and designing and evaluating strategies to address vaccine hesitancy and increase vaccine uptake. Existing validated measures assessing vaccine hesitancy focus primarily on confidence in vaccines and the system that delivers them. However, empirical and theoretical work has stated that complacency (not perceiving diseases as high risk), constraints (structural and psychological barriers), calculation (engagement in extensive information searching), and aspects pertaining to collective responsibility (willingness to protect others) also play a role in explaining vaccination behavior. The objective was therefore to develop a validated measure of these 5C psychological antecedents of vaccination. Methods and Findings Three cross-sectional studies were conducted. Study 1 uses factor analysis to develop an initial scale and assesses the sub-scales’ convergent, discriminant, and concurrent validity (N = 1,445, two German convenience-samples). In Study 2, a sample representative regarding age and gender for the German population (N = 1,003) completed the measure for vaccination in general and for specific vaccinations to assess the potential need for a vaccine-specific wording of items. Study 3 compared the novel scale’s performance with six existing measures of vaccine hesitancy (N = 350, US convenience-sample). As an outcome, a long (15-item) and short (5-item) 5C scale were developed as reliable and valid indicators of confidence, complacency, constraints, calculation, and collective responsibility. The 5C sub-scales correlated with relevant psychological concepts, such as attitude (confidence), perceived personal health status and invulnerability (complacency), self-control (constraints), preference for deliberation (calculation), and communal orientation (collective responsibility), among others. The new scale provided similar results when formulated in a general vs. vaccine-specific way (Study 2). In a comparison of seven measures the 5C scale was constantly among the scales that explained the highest amounts of variance in analyses predicting single vaccinations (between 20% and 40%; Study 3). The present studies are limited to the concurrent validity of the scales. Conclusions The 5C scale provides a novel tool to monitor psychological antecedents of vaccination and facilitates diagnosis, intervention design and evaluation. Its short version is suitable for field settings and regular global monitoring of relevant antecedents of vaccination.