Background: This study was carried out to determine factors perceived to impact on medication administration errors and possible solutions to such errors in medical and surgical units of public hospitals in Gauteng Province, South Africa. More data on this challenge to patient health are needed from low- and middle-income countries like South Africa.Methods: A mixed-methods research design with a sequential approach was used. Data were gathered among 683 (n=280) medication administrators using self-report surveys, and 16 (n=15) nursing unit managers using semi-structured individual interviews.Results: Causes of medication error related to communication, human, environmental and medication factors were considered to have a moderate risk. Workload (M=3.39; SD 0.91), stock problems (M=3.18; SD 0.96) and illegible prescriptions (M=3.05; SD 1.09) pose the greatest threats to medication administration safety. Most participants (n=184; 71.1%) agreed that medication errors never or rarely occurred in their units. The majority of respondents graded overall patient safety as excellent or very good (n=161; 61.5%). With regard to safety culture, nurses felt that they are actively attempting to improve medication safety (n=239; 90.5%), that people support one another in the unit (n=216; 80%), and that their procedures and systems are good at preventing errors (n=210; 80.2%). Participants felt that medication administration errors were rarely reported, and the most apparent reason for not reporting medication administration errors was fear and administrative response. Safety culture items were correlated with medication error incidence, grade of overall patient safety and reasons for non-reporting. Qualitative findings supported the quantitative data, adding knowledge, skill and attitude of staff as further threats to medication administration safety. Adherence to protocols, auditing, education and training, collaboration and support, communication, awareness of changes, resource management and time management were identified as possible solutions to medication administration errors.Conclusions: Solutions aimed at mitigating medication errors should be based on causes identified within a specific context. In the Gauteng Province of South Africa, multidisciplinary collaboration and communication; support of nurses by the hospital administration; hospital systems, procedures and initiatives; better resource management and improved pharmacological training could be seen as the foundation for improved medication administration safety.