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Objectives Personal factors, especially attitude, have been implicated in the utilization of health care services, and in access to medical treatment. There is little information on the attitudes of the general public in South Africa towards medications and whether attitudes differ across population groups or among the different users of the health care system. This study aimed to determine the general attitude of a local population to medications, self-care orientation and health professional contact, and whether differences existed between age groups, gender and race groups. Methods We carried out a randomized, cross-sectional quantitative study via telephonic questionnaire survey (adapted from a previous study) of a sample of 1132 telephone numbers. The setting was the Durban Metropolitan Area, KwaZulu-Natal, South Africa. Key findings A total of 500 (44.2%) people responded. The majority had a positive attitude towards medication. An increase in age resulted in increased medication use. Females were more likely than males to use medication and seek professional health care (P = 0.0406). Most of the respondents (86.0%) were self-care-orientated and displayed moderate medication knowledge (46.2%). Some 295 (59.0%) of the 500 respondents had visited a pharmacy within the last 6 months. Conclusions Health care professionals can adopt an informed approach to address the needs of the population with regard to medication, by targeting groups more likely to use medication (females and the older age group). In addition, gaps in medication knowledge were identified which could be used for health-promotion interventions by health care workers.