OBJECTIVES: Unintentional non-adherence has been characterized as passively inconsistent medication-taking behavior (negligence, carelessness, or forgetfulness). Our objective was to study the prevalence and predictors of unintentional non-adherence. METHODS: We conducted a cross-sectional survey of adults with asthma, hypertension, diabetes, hyperlipidemia, osteoporosis, or depression from the Harris Chronic Disease Panel. A total of 24,071 adults self-identified themselves as adherent to prescription medications for their index disease and answered three questions on unintentional non-adherence: During the past six months, did you 1) ever forget to take the medication; 2) run out of the medication; and 3) were careless at times about taking the medication? Logistic regression was used to model predictors of each unintentional non-adherence behavior. Independent variables were demographics, index chronic disease, total number of prescription medications, self-rated health, and multi-item scales assessing perceived need for medications, medication concerns, and perceived medication affordability. RESULTS: For the index disease: 62% forgot to take a medication, 37% had run out of the medication, and 23% were careless about taking the medication. Common multivariate predictors (p < .001) of the three behaviors were: 1) lower perceived need for medications; 2) more medication affordability problems; 3) worse self-rated health; 4) diabetes or osteoporosis (relative to hypertension); and 5) younger age. Unique predictors of 'forgot to take medications' were higher concerns about the index medication and male gender. Unique predictors of 'run out of medications' were non-white race, asthma, and higher number of total prescription medications. The unique predictor of 'being careless' was higher medication concerns. CONCLUSIONS: Unintentional non-adherence does not appear to be random and is predicted by medication beliefs, chronic disease, and sociodemographics. Interventions addressing unintentional non-adherence should not simply focus on reminders, but should also address medication beliefs related to perceived need, concerns, and medication affordability.