Objectives: To synthesise contributing factors leading to medicine-related problems (MRPs) in adult patients with cardiovascular diseases and/or diabetes mellitus from their perspectives. Design: A systematic literature review of qualitative studies regarding the contributory factors leading to MRPs, medication errors and non-adherence, followed by a thematic synthesis of the studies. Data sources: We screened Pubmed, EMBASE, ISI Web of Knowledge, PsycInfo, International Pharmaceutical Abstract and PsycExtra for qualitative studies (interviews, focus groups and questionnaires of a qualitative nature). Review methods: Thematic synthesis was achieved by coding and developing themes from the findings of qualitative studies. Results: The synthesis yielded 21 studies that satisfied the inclusion and exclusion criteria. Three themes emerged that involved contributing factors to MRPs: patient-related factors including socioeconomic factors (beliefs, feeling victimised, history of the condition, lack of finance, lack of motivation and low self-esteem) and lifestyle factors (diet, lack of exercise/time to see the doctor, obesity, smoking and stress), medicine-related factors (belief in natural remedies, fear of medicine, lack of belief in medicines, lack of knowledge, non-adherence and polypharmacy) and condition-related factors (lack of knowledge/understanding, fear of condition and its complications, and lack of control). Conclusions: MRPs represent a major health threat, especially among adult patients with cardiovascular diseases and/or diabetes mellitus. The patients' perspectives uncovered hidden factors that could cause and/or contribute to MRPs in these groups of patients.