Self-reported medication adherence is known to overestimate true adherence. However, little is known about patient factors that may contribute to the upward bias in self-reported medication adherence. The objective of this study is to examine whether demographic, behavioral, medication and mood factors are associated with being a false-positive self-reported adherer (FPA) to antihypertensive drug treatment. We studied 175 patients (mean age: 50 years; 57% men) from primary-care clinics starting antihypertensive drug treatment. Self-reported adherence (SRA) was measured with the Medication Adherence Report Scale (MARS) and by the number of drug doses missed in the previous week/month, and compared with pill count adherence ratio (PCAR) as gold standard. Data on adherence, demographic, behavioral, medication and mood factors were collected at baseline and every 3 months up to 1 year. FPA was defined as being a non-adherer by PCAR and an adherer by self-report. Mixed effect logistic regression was used for the analysis. Twenty percent of participants were FPA. Anxiety increased (odds ratio (OR): 3.00; P = 0.01), whereas smoking (OR: 0.40; P = 0.03) and drug side effects (OR: 0.46, P = 0.03) decreased the probability for FPA by MARS. Education below high-school completion increased the probability of being an FPA as measured by missing doses in the last month (OR: 1.66; P = 0.04) and last week (OR: 1.88; P = 0.02). The validity of SRA varies significantly according to drug side effects, behavioral factors and patient's mood. Careful consideration should be given to the use of self-reported measures of adherence among patients likely to be false-positive adherers.