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This baseline assessment was conducted in order to document the knowledge, awareness and practice of pharmacovigilance systems among public health care professionals (HCPs) in the Eastern Cape (EC) Province of South Africa, as a key to understanding the strategies required for the roll-out of a pharmacovigilance programme. A semi-structured, researcher-administered questionnaire was used to interview seven key informants and 53 HCP. Informal conversations and observations were also conducted with various other HCPs to supplement the collected information. Findings from this baseline assessment revealed limited knowledge, awareness and practice around pharmacovigilance systems and processes among HCPs and key informants. They further highlighted gaps that can inform planning for training in the province. In conclusion, the baseline assessment found gaps that indicate the need for an appropriate training intervention of all relevant HCPs impacted by the roll-out of the decentralised pharmacovigilance programme in order to ensure the successful implementation of the programme in the EC Province of South Africa.