OBJECTIVES: The "healthy adherer effect" posits that part of the association between non-adherence and suboptimal health outcomes is the possible confounding effect of worse lifestyle behaviors of non-adherers. Our objective was to test the "healthy adherer effect" among US adults with chronic disease.  METHODS: We conducted a cross-sectional survey of 22,070 adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, GERD, depression, or anxiety from the Harris Chronic Disease Panel. Respondents were classified into one of three mutually-exclusive categories: (1) persisters (i.e., currently taking medication); (2) non-persisters (i.e., discontinued medication in the past year); and (3) non-fulfillers (i.e., did not obtain the first fill for a new prescription in the past year). Respondents also completed items on life style behaviors: weight and height to derive BMI, smoking status; alcohol use; physical exercise; seatbelt use; and receipt of an influenza vaccination in the past year. Linear and logistic regression was used to model individual lifestyle behaviors on self-reported adherence status controlling for demographic characteristics. RESULTS: Multivariate regressions revealed no statistically-significant associations between adherence status and BMI (continuous), weekly-moderate exercise, weekly-vigorous exercise, binge drinking, and obesity as defined by the BMI. Multivariate regressions revealed that non-persisters and non-fulfillers were significantly less likely to report having a flu shot in the past year (OR=0.76 and 0.73, respectively). Compared to persisters, non-persisters were more likely to be current smokers (OR=1.19, p=.0043) and were less likely to always use seat belts (OR=0.80, p=.0009). CONCLUSIONS: In this Internet sample of 22,070 adults with chronic disease, we found mixed evidence for a "healthy adherer effect." Non-persisters and non-fulfillers differed from persisters on some, but not all, lifestyle behaviors. Future research should link both adherence behaviors and life-style behaviors to risk of mortality and hospitalization.