ObjectivesTo (1) estimate the combined risks of cigarette smoking and physical inactivity for chronic disease, disability and depressive symptoms and (2) determine whether risks associated with these behaviours are additive or synergistic.Design and settingLongitudinal observational population study using data from Waves 2 (2004/2005) through 8 (2016/2017) of the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults in England.Participants6425 men and women aged ≥52 years (mean (SD) 65.88 (9.34) years) at baseline.Main outcome measuresSmoking status (never, former, current) and level of physical activity (high, defined as moderate/vigorous physical activity (MVPA) more than once a week; low, defined as MVPA once a week or less) were self-reported at Wave 2 baseline. Self-rated health, limiting long-standing illness, chronic conditions (coronary heart disease (CHD), stroke, cancer, chronic lung disease) and depressive symptoms were reported in each biennial wave.ResultsBoth smoking and low levels of physical activity were associated with increased risk of incident health problems over the 12-year follow-up period. Current smokers with low levels of physical activity had especially high risks of developing fair/poor self-rated health, CHD, stroke, cancer and chronic lung disease compared with highly active never smokers (adjusted relative risk range 1.89–14.00). While additive effects were evident, tests of multiplicative interactions revealed no evidence of large synergistic effects of smoking and low physical activity (Bayes factor range 0.04–0.61), although data were insensitive to detect smaller effects.ConclusionsAmong older adults in England, there was no evidence of large synergistic effects of smoking and low levels of physical activity on risk of developing chronic disease or depressive symptoms over 12 years. However, additive effects of smoking and low levels of physical activity were evident, underscoring the importance of each of these lifestyle risk behaviours for disease onset.