For decades, scholars have been exploring persistent inequalities in health by studying the roles of origin and destination socioeconomic positions (SEP), and the importance of social mobility trajectories from childhood to adult life in individuals’ wellbeing. However, this literature does not produce consistent and systematic findings on the relative importance of origin and destination SEP and independent social mobility effects. One of the main reasons for this is a set of methodological choices and decisions which researchers make. Arguably, one of the most critical aspects of research design is the operationalisation of SEP and the selection of health outcomes, usually without accounting for initial values of the health indicators employed. Using a nationally representative longitudinal dataset (Add Health) for the United States and diagonal reference models, in the present study, we examine how the choice of SEP in terms of educational, occupational, and income attainment, and the choice of health measures in terms of obesity, depressive symptoms, and self-rated health, influence findings on the origin and destination effects, as well as the health implications of social mobility. We also address the health selection problem by explicitly accounting for adolescents’ health in terms of each health outcome considered. Our results indicate that both choosing SEP and health measures, and accounting for social mobility and adolescent health have a noticeable impact on the relative importance of social origin and destination positions for health outcomes. We do not find evidence that social mobility has an independent effect on health, or that individuals’ previous health status moderates this association.