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This study reports initial results of the development of the SIAM, a non-adherence risk assessment system for tacrolimus and sirolimus for the pediatric kidney transplant population. Forty-eight youths between 10 and 25 yr of age diagnosed with chronic kidney disease or a kidney transplant used an electronic pill bottle (EM; time stamps each bottle opening) to dispense their medication for at least 30 days or until their next clinic appointment. Youth also completed a self-report adherence measure, and standard deviations were calculated for the last four medication serum trough levels obtained for each patient. Estimation models were developed for each medication (i.e., SIAMTACRO and SIAMSIRO) to assign weights to these clinically available adherence measures (self-report and trough levels) for the calculation of a non-adherence risk composite score. SIAMTACRO models included both self-report and tacrolimus trough levels and significantly predicted EM. For sirolimus, the model predictive of adherence as measured by EM consisted of the standard deviation of sirolimus trough levels only (SIAMSIRO). Non-adherence risk can be effectively assessed using clinically available assessment tools. However, the best methods for using self-report and trough levels to predict non-adherence likely differ based on the medication for which adherence is being assessed.