Cytochrome P450 (CYP)3A is involved in the metabolism of more than 50% of prescribed drugs, and reports indicate that 70% of CYP3A inducers are also CYP3A inhibitors, thereby complicating the interpretation of induction based DDI potential and reducing the confidence in clinical outcome extrapolation for co-regulated enzymes such as CYP2C8, 2C9 and 2C19. While the preclinical assessment of CYP3A4 induction has been conducted extensively, the evaluation of CYP2C induction is hindered by low dynamic response in standard monoculture hepatocyte models, which may prompt additional clinical DDI investigations. This study was aimed to characterize the induction potential of CYP2C enzymes in all human hepatocyte triculture model (HTC), a two-dimensional hepatic system with human primary hepatocytes, stromal, and endothelial cells. The in vitro induction potential of known inducers of CYP2C8, CYP2C9, CYP2C19 and CYP3A was assessed using the HTC model. In addition, hepatocytes from a single donor were plated in the sandwich culture (SC) model for direct comparison of induction endpoints and the induction parameters were used for simulating clinical PK implications. RNA-seq results showed distinct basal expression differences in CYPs, transporters and transcription factors between both models, potentially suggesting better recapitulation of native liver hepatocytes in the HTC model. Compared to SC, the HTC model showed robust induction of CYP2C. By incorporating the induction parameters obtained from the HTC model into PBPK models, an excellent correlation was obtained relative to clinical outcomes for CYP2C8, CYP2C9, CYP2C19 and CYP3A4. Overall, this study provides a potential approach to quantitatively assess CYP2C-induction risk preclinically.