OBJECTIVES: Compliance and treatment duration can have a significant impact on costs and health outcomes in health-economic assessments, especially in high-cost therapy areas such as oncology. The objective of this study was to systematically review different methods for addressing treatment compliance and discontinuation in oncology economic models, critique the identified methodologies, and highlight best practices. METHODS: A systematic review was undertaken to investigate the different methods that could be used to include compliance and treatment discontinuation in economic modelling in oncology populations. MEDLINE, Embase, EconLit and the Cochrane Library (from 2000 onwards), and technology assessment documents and manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE) were searched for economic analyses which mentioned compliance or discontinuation. Results were filtered using pre-specified selection criteria and data extracted into a pre-defined template. RESULTS: Sixty-eight publications of 51 models were included, comprising 20 journal publications and 48 technology appraisal documents. Possible methods were divided into ten categories. Seven studies mentioned discontinuations, but did not include a modelling approach. There was a lack of consensus regarding the methods applied. Twenty studies varied dose or discontinuation rate in sensitivity analyses, although impact on overall outcomes was rarely explored. Dose intensity was most often adopted from clinical trials. Effects on the overall outcomes by inclusion of discontinuations or dose intensity adjustments were rarely discussed. Overall, the authors of included publications poorly justified their methods regarding compliance assumptions. CONCLUSIONS: The combination of several methods could improve accuracy of modelling discontinuations. Discontinuations should affect three aspects of the model: transition probabilities, costs and effects. Clear explanations and justification of the included parameter assumptions should also be improved in NICE submissions to enhance likelihood of positive recommendation. Standardised guidelines could raise more attention to compliance in economic modelling and could improve the accuracy of economic models.