In-sewer stability of illicit drug biomarkers has been evaluated by several reactor-based studies, but less has beendone in sewer pipes. Experiments conducted in sewer pipes have advantages over lab-scale reactors in providing more realisticbiomarker stability due to theflow and biological dynamics. This study assessed the transportation and transformation of sevenillicit drug biomarker compounds in a pilot-scale rising main and a gravity sewer pipe. Biomarkers presented diverse stabilitypatterns in the pilot sewers, based on which a drug transformation model was calibrated. This model was subsequently validatedusing transformation data sets from the literature, aiming to demonstrate the predictability of the pilot-based transformationcoefficients under varying sewer conditions. Furthermore, transformation coefficients forfive investigated biomarkers weregenerated from four studies, and their prediction capabilities under the pilot-sewer conditions were jointly assessed usingperformance 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 besimulated in the transformation model. Overall, the transformation model calibrated using the pilot-sewer data is a credible toolfor the application of wastewater-based epidemiology.