*Purpose: The objective of this evaluation was to estimate the cost of implementation and the cost-effectiveness of a person-level intervention called SystemCHANGE^TM .

*Methods: To estimate the intervention costs, a direct measure micro-costing approach was used following key informant interviews with project champions and a review of implementation expenditures. Cost-effectiveness was calculated by comparing the incremental implementation costs and healthcare costs associated with non-adherence to the incremental percent adherent, defined as the percent of patients who took greater or equal to 85% of their medication doses, for each pairwise comparison.

*Results: Medication adherence was improved at 6 months for the SystemCHANGE™ intervention (median 0.91, IQR 0.76‐0.96) compared to attention control (median 0.67, IQR 0.52‐0.72) with a marked difference in medians (0.24, 95% CI 0.13‐0.30, P < .001). The intervention was low-resource to implement, costing approximately $520 to implement per patient, and was associated with significant improvements in medication adherence.

*Conclusions: Interventions to improve medication non-adherence in transplantation have recently moved from a focus on motivation and intention, to a focus on person-level quality improvement strategies to link adherence to established daily routines, environmental cues and supportive people. In this study, the implementation costs were more than outweighed by the expected healthcare savings associated with improvements in adherence. This person-level intervention is a low cost, efficacious intervention associated with significant statistical and clinical improvements in medication adherence in adult kidney transplant recipients.

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