Interactions between early life and adult insults on lung function decline are not well understood, with most studies investigating prebronchodilator (pre-BD) FEV decline. To investigate relationships between adult risk factors and pre- and post-BD lung function decline and their potential effect modification by early life and genetic factors. Multiple regression was used to examine associations between adult exposures (asthma, smoking, occupational exposures, traffic pollution, and obesity) and decline in both pre- and post-BD spirometry (forced expiratory volume in 1 s FEV , forced vital capacity FVC, and FEV /FVC) between ages 45 and 53 years in the Tasmanian Longitudinal Health Study (  = 857). Effect modification of these relationships by childhood respiratory risk factors, including low childhood lung function and GST (glutathione S-transferase) gene polymorphisms, was investigated. Baseline asthma, smoking, occupational exposure to vapors/gases/dusts/fumes, and living close to traffic were associated with accelerated decline in both pre- and post-BD FEV . These factors were also associated with FEV /FVC decline. Occupational exposure to aromatic solvents was associated with pre-BD but not post-BD FEV decline. Maternal smoking accentuated the effect of personal smoking on pre- and post-BD FEV decline. Lower childhood lung function and having the GSTM1 null allele accentuated the effect of occupational exposure to vapors/gases/dusts/fumes and personal smoking on post-BD FEV decline. Incident obesity was associated with accelerated decline in FEV and more pronounced in FVC. This study provides new evidence for accentuation of individual susceptibility to adult risk factors by low childhood lung function, GSTM1 genotype, and maternal smoking.