e-Prescribing is designed to assist in facilitating safe and appropriate prescriptions for patients. Currently, it is unknown to what extent e-prescribing for opioids influences experiences and outcomes. To address this gap, a rapid scoping review was conducted. This rapid scoping review aims to (1) explore how e-prescribing has been used clinically; (2) examine the effects of e-prescribing on clinical outcomes, the patient or clinician experience, service delivery, and policy; and (3) identify current gaps in the present literature to inform future studies and recommendations. A rapid scoping review was conducted following the guidance of the JBI 2020 scoping review methodology and the World Health Organization guide to rapid reviews. A comprehensive literature search was completed by an expert librarian from inception until November 16, 2022. Three databases were electronically searched: MEDLINE (Ovid), Embase (Ovid), and Scopus (Elsevier). The search criteria were as follows: (1) e-prescribing programs targeted to the use or misuse of opioids, including those that were complemented or accompanied by clinically focused initiatives, and (2) a primary research study of experimental, quasi-experimental, observational, qualitative, or mixed methods design. An additional criterion of an ambulatory component of e-prescribing (eg, e-prescribing occurred upon discharge from acute care) was added at the full-text stage. No language limitations or filters were applied. All articles were double screened by trained reviewers. Gray literature was manually searched by a single reviewer. Data were synthesized using a descriptive approach. Upon completing screening, 34 articles met the inclusion criteria: 32 (94%) peer-reviewed studies and 2 (6%) gray literature documents (1 thesis study and 1 report). All 33 studies had a quantitative component, with most highlighting e-prescribing from acute care settings to community settings (n=12, 36%). Only 1 (3%) of the 34 articles provided evidence on e-prescribing in a primary care setting. Minimal prescriber, pharmacist, and clinical population characteristics were reported. The main outcomes identified were related to opioid prescribing rates, alerts (eg, adverse drug events and drug-drug interactions), the quantity and duration of opioid prescriptions, the adoption of e-prescribing technology, attitudes toward e-prescribing, and potential challenges with the implementation of e-prescribing into clinical practice. e-Prescribing, including key features such as alerts and dose order sets, may reduce prescribing errors. This rapid scoping review highlights initial promising results with e-prescribing and opioid therapy management. It is important that future work explores the experience of prescribers, pharmacists, and patients using e-prescribing for opioid therapy management with an emphasis on prescribers in the community and primary care. Developing a common set of quality indicators for e-prescribing of opioids will help build a stronger evidence base. Understanding implementation considerations will be of importance as the technology is integrated into clinical practice and health systems.