INTRODUCTION:: Adenocarcinoma in situ (AIS), formerly bronchioloalveolar carcinoma, is an uncommon subtype of lung adenocarcinoma and accounts for approximately 3% to 4% of lung cancers. Compared with other lung cancer histologies, AIS patients are less likely to be smokers, yet associations with other lung cancer risk factors and differences by sex have not been determined. METHODS:: A total of 338 AIS patients and frequency-matched controls from the parent study (cases = 6039, controls = 2073) were included in these analyses. Odds ratios and 95% confidence intervals as estimates of the relative risk were obtained from multivariable unconditional logistic regression analyses. RESULTS:: Risk of AIS was associated with ever smoking (OR = 2.7, 95% confidence intervals: 2.1, 3.6), increased 20% to 30% for each 10-year increase in pack-years of smoking and decreased with increased years since quitting (p for trend <0.0001). There was no evidence that risk differed by sex but there was some suggestion that risk may differ by exposure to asbestos and by second-hand tobacco smoke exposure in whites. CONCLUSION:: There is an association between AIS and smoking, which is smaller in magnitude than the association between other subtypes of non-small-cell lung cancer and smoking. Our findings suggesting that effects may differ by exposure to asbestos and second-hand tobacco smoke should be interpreted conservatively and warrant validation and further evaluation in larger studies of AIS.