OBJECTIVES:  The objectives of this study were to (1) describe the medication experiences of the U.S. adult population, (2) identify distinct segments based upon these experiences, and (3) identify differences among segments, including geographic variation. METHODS:  Data were collected via an on-line survey, sent to a sample of adults residing in the United States, between April 28 and June 22, 2015. A total of 26,173 usable responses were received, with at least 500 from each of the 50 states and the District of Columbia. Multiple-item constructs were tested for convergent and discriminant validity using factor analysis. Identification of segments was accomplished through a two-step clustering algorithm, with an agglomerative hierarchical clustering method, a log-likelihood distance measure, and the silhouette measure for assessing cohesion and separation. RESULTS:  Factor analysis showed that multiple-item constructs were valid. The most suitable cluster arrangement utilizing the silhouette measure of cohesion and separation consisted of preferred cognitive styles and medication belief differentials. The approach yielded twelve distinct segments composed of variations of four different ‘Cognitive Styles’ (Conceptual, Ideal, Practical, Social) and four different Medication Beliefs (Firm Savior, Moderate Savior, Moderate Burden, Firm Burden). These segments showed differences in patient activation, information engagement, information apprehension, information gathering, information processing, health behaviors, demographic characteristics, health characteristics, cultural and religious characteristics, and experiences with pharmacists and pharmacist services. CONCLUSIONS:  The findings revealed distinct segments in the medication experience of U.S. adults in terms of concrete versus relational information processing styles, detail-oriented versus big picture decision-making preferences, and perceptions of medications that ranged from being a life-burden to being a life-savior. Notable interstate variation was observed for medication belief differentials. The findings can be useful for incorporating components of the medication experience into patient care processes, including the building of systems for identifying and matching patients with suitable providers based upon preferences and capabilities.