AIM : To align predicted and measured CYP2C19 phenotype in a South African cohort. MATERIALS AND METHODS : Genotyping of CYP2C19*2, *3, *9, *15, *17, *27 and *28 was performed using PCR-RFLP, and an Activity Score (AS) system was used to predict phenotype.True phenotype was measured using plasma concentrations of omeprazole and its metabolite 5’-hydroxyomperazole. RESULTS : Partial genotype-phenotype discrepancies were reported, and an adapted AS system was developed, which showed a marked improvement in phenotype prediction. Results highlight the need for a more comprehensive CYP2C19 genotyping approach to improve prediction of omeprazole metabolism. CONCLUSION : Evidence for the utility of a CYP2C19 AS system is provided, for which the accuracy can be further improved by means of comprehensive genotyping and substrate specific modification. ; Departments of Pharmacology and Immunology, University of Pretoria; the National Research Foundation of South Africa (NRF) grant numbers FA2006032700005 and TK2006051500005; the National Health Laboratory Services of South Africa (NHLS); the South African Medical Research Council (SAMRC) Extramural Unit for Inflammation and Immunity, and Ampath Laboratories, South Africa. ; http://www.futuremedicine.com/loi/pgs ; 2016-08-31 ; hb2015