Chemotherapy-induced peripheral neuropathy (CIPN) is a common and potentially dose-limiting side effect of neurotoxic chemotherapies. No therapies are available to prevent CIPN. The small number of positive randomized clinical trials (RCTs) evaluating preventive therapies for CIPN provide little guidance to inform the design of future trials. Moreover, the lack of consensus regarding major design features in this area poses challenges to development of new therapies. An Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION)-Consortium on Clinical Endpoints and Procedures for Peripheral Neuropathy Trials (CONCEPPT) meeting attended by neurologists, oncologists, pharmacists, clinical trialists, statisticians, and regulatory experts was convened to discuss design considerations and provide recommendations for CIPN prevention trials. This article outlines considerations related to design of RCTs that evaluate preventive therapies for CIPN including (1) selection of eligibility criteria (e.g., cancer types, chemotherapy types, inclusion of preexisting neuropathy); (2) selection of outcome measures and endpoints, including those that incorporate alterations in chemotherapy dosing, which may affect the rate of CIPN development and its severity; (3) potential effects of the investigational therapy on the efficacy of chemotherapy; and (4) sample size estimation. Our hope is that attention to the design considerations and recommendations outlined in this article will improve the quality and assay sensitivity of CIPN prevention trials and thereby accelerate the identification of efficacious therapies.