The purpose of the present study was to examine whether cytochrome P450 2C19 (CYP2C19) in carriers of the CYP2C19*17 allele is inhibited in vivo by oral contraceptives (OC). Retrospective CYP2C19 phenotyping according to omeprazole : 5‐OH‐omeprazole molar 3 h plasma metabolic ratios (MR) from a population (n = 222) genotyped as CYP2C19*1/*1, CYP2C19*1/*17 and CYP2C19*17/*17 was analysed. Furthermore, 30 women genotyped as CYP2C19*1/*1 (n = 11), CYP2C19*1/*17 (n = 11) and CYP2C19*17/*17 (n = 8) were prospectively CYP2C19 phenotyped during the administration of OC and again after a minimum 5 days break from OC. We found a significantly higher MR in the CYP2C19*1/*1 genotype group that took OC (n = 48) compared with women who did not take OC (n = 31; geometric mean 1.37 vs 0.83, respectively; P < 0.05). However, in the CYP2C19*1/*17 genotype group, the geometric means of the MR in the 37 women taking OC and the 20 women not taking OC were 0.67 and 0.46, respectively (P > 0.05). In the CYP2C19*1/*1 panel of the prospective cross‐over study, we found a significantly higher MR while women were taking the OC compared with the MR during the OC break (geometric mean 1.21 vs 0.91, respectively; P = 0.0123). However, in the CYP2C19*1/*17 group, the geometric means of the MR with and without OC were 0.77 and 0.65, respectively, compared with 1.05 and 0.79, respectively, in the CYP2C19*17/*17 group (P = 0.20 and 0.17, respectively). In conclusion, we have shown that OC intake inhibits CYP2C19 in homozygous carriers of the CYP2C19 wild type but that the inhibition is not significant in heterozygous and homozygous carriers of the CYP2C19*17 allele.