BACKGROUND CONTEXT: Whiplash-associated disorders (WAD) and neck pain and associated disorders (NAD) are prevalent conditions that impact society and impose a significant economic burden on health-care systems. Health economic evidence on WAD and NAD interventions has been sparse: only three economic evaluations of interventions for NAD were identified by the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (NPTF). An updated overview is needed to inform health-care policy and guidelines. PURPOSE: This study aimed to determine the cost-effectiveness of interventions for grades I-III WAD and NAD in children and adults. STUDY DESIGN: Systematic review of health economic literature, best-evidence synthesis. METHODS: We systematically searched CINAHL, the Cochrane economic databases (Health Technology Assessment, NHS Economic Evaluation Database), EconLit, EMBASE, MEDLINE, PsycINFO, and Tufts CEA Registry from 2000 to 2015 for economic evaluations of WAD and NAD interventions. We appraised relevant evaluations using the Scottish Intercollegiate Guidelines Network Methodology Criteria for Economic Evaluations. We extracted data, including mean costs (standardized to 2013 Canadian dollars [CAD]) and quality-adjusted life years (QALYs), from studies with adequate methodological quality. We recalculated cost-effectiveness statistics based on the standardized currency using a willingness-to-pay of CAD $50,000 per additional QALY. Funding was provided by the Ministry of Finance. RESULTS: Our search identified 1,616 citations. Six studies fulfilled our selection criteria, including three studies previously reviewed by the NPTF. Structured education appears cost-effective for adults with WAD. For adults with NAD, acupuncture added to routine medical care; manual therapy; multimodal care that includes manual therapy; advice and exercise; and psychological care using cognitive-behavioral therapy appear cost-effective. In contrast, adding manual therapy or diathermy to advice and exercise; multimodal care by a physiotherapist or physician; and behavioral-graded activity do not appear cost-effective for adults with NAD. CONCLUSIONS: Our review adds to the findings of the NPTF. Recent evidence suggests that structured education is cost-effective for WAD, whereas advice and exercise and multimodal care that include manual therapy are cost-effective for NAD. Obtaining more robust health economic evidence for non-invasive interventions for WAD and NAD in children and adults remains an essential research priority.