INTRODUCTION: This study examined whether psychosocial variables influenced patients' perception and experience of side effects of their medicines, how they coped with these experiences and the impact on medication adherence behaviour. METHODS: A hospital-based mixed methods study using quantitative and qualitative approaches was conducted with hypertensive patients. Participants were asked about side effects, medication adherence, common psychological symptoms and coping mechanisms with the aid of standard questionnaires and an interview guide. RESULTS: The experiences of side effects-such as palpitations, frequent urination, recurrent bouts of hunger, erectile dysfunction, dizziness, cough, physical exhaustion-were categorized as no/low (39.75 %), moderate (53.0 %) and high (7.25 %). Significant relationships between depression (chi2 = 24.21, p < 0.0001), anxiety (chi2 = 42.33, p < 0.0001), stress (chi2 = 39.73, p < 0.0001) and side effects were observed. A logistic regression model using the adjusted results for this association is reported-depression [OR = 1.9 (1.03-3.57), p = 0.04], anxiety [OR = 1.5 (1.22-1.77), p < or = 0.001] and stress [OR = 1.3 (1.02-1.71), p = 0.04]. Side effects significantly increased the probability of individuals to be non-adherent [OR = 4.84 (95 % CI 1.07-1.85), p = 0.04] with social factors, media influences and attitudes of primary care givers further explaining this relationship. Personal adoption of medication modifying strategies, espousing the use of complementary and alternative treatments and interventions made by clinicians were the main forms of coping with side effects. DISCUSSION: Results from this study show that, in addition to a biomedical approach, the experience of side effects has biological, social and psychological interrelations. The results offer more support for the need for a multi-disciplinary approach to healthcare where all forms of expertise are incorporated into health provision and patient care.