In-sewer stability of illicit drug biomarkers has been evaluated by several reactor-based studies, but less has been done in sewer pipes. Experiments conducted in sewer pipes have advantages over lab-scale reactors in providing more realistic biomarker stability due to the flow and biological dynamics. This study assessed the transportation and transformation of seven illicit drug biomarker compounds in a pilot-scale rising main and a gravity sewer pipe. Biomarkers presented diverse stability patterns in the pilot sewers, based on which a drug transformation model was calibrated. This model was subsequently validated using transformation data sets from the literature, aiming to demonstrate the predictability of the pilot-based transformation coefficients under varying sewer conditions. Furthermore, transformation coefficients for five investigated biomarkers were generated from four studies, and their prediction capabilities under the pilot-sewer conditions were jointly assessed using performance statistics. The transformation model was successful in simulating the in-sewer stability for most illicit drugs. However, further study is required to delineate the sources and pathways for those compounds with potential formations to be simulated in the transformation model. Overall, the transformation model calibrated using the pilot-sewer data is a credible tool for the application of wastewater-based epidemiology.