Multimorbidity is associated with adverse outcomes, yet research on the determinants of its incidence is lacking. We investigated which sociodemographic, health, and individual lifestyle (eg, physical activity, smoking behavior, body mass index) characteristics predict new cases of multimorbidity.We used data from 4,564 participants aged 50 years and older in the English Longitudinal Study of Aging that included a 10-year follow-up period. Discrete time-to-event (complementary log-log) models were constructed for exploring the associations of baseline characteristics with outcomes between 2002-2003 and 2012-2013 separately for participants with no initial conditions (n = 1,377) developing multimorbidity, any increase in conditions within 10 years regardless of initial conditions, and the impact of individual conditions on incident multimorbidity.The risks of developing multimorbidity were positively associated with age, and they were greater for the least wealthy, for participants who were obese, and for those who reported the lowest levels of physical activity or an external locus of control (believing that life events are outside of one's control) for all groups regardless of baseline conditions (all linear trends <.05). No significant associations were observed for sex, educational attainment, or social detachment. For participants with any increase in conditions (n = 4,564), a history of smoking was the only additional predictor. For participants with a single baseline condition (n = 1,534), chronic obstructive pulmonary disease (COPD), asthma, and arrhythmia showed the strongest associations with subsequent multimorbidity.Our findings support the development and implementation of a strategy targeting the prevention of multimorbidity for susceptible groups. This approach should incorporate behavior change addressing lifestyle factors and target health-related locus of control.