The WHO identified Pharmacy and Therapeutics Committees (PTCs) as a pivotal model to promote rational medicine use in hospitals. This matches a key South African (SA) government objective to establish PTCs in all hospitals to ensure rational, efficient and cost-effective use of medicines. However, documentation on the functionality of PTCs in public hospitals in SA is limited. Areas covered: This study aimed to address this. A 3-phased mixed methods approach involving questionnaires, observations of PTC meetings and semi-structured interviews was used. The findings were converged during the interpretation phase. Expert commentary: Most professionals were represented in the PTCs, with variations across hospitals. Membership of PTCs included a pharmacist, who in the majority of cases was the secretary. PTC activities included dissemination of decisions (100%) and formulary management (89.5%). However, reporting of adverse drug reactions (ADRs) and medication errors was typically poor at all hospital levels. Lack of expertise of pharmacoeconomic analysis and evidence-based decision-making in formulary management was identified as a key challenge in formulary management. In conclusion, future programmes should strengthen PTCs in specialised aspects of formulary management. Further training in the principles of pharmacovigilance is needed to enhance ADR reporting, as well as to ensure compliance with both WHO and provincial guidelines.