Article-level measures of publication impact (alternative metrics or altmetrics) can help authors and other stakeholders assess engagement with their research and the success of their communication efforts. The wide variety of altmetrics can make interpretation and comparative assessment difficult; available summary tools are either narrowly focused or do not reflect the differing values of metrics from a stakeholder perspective. We created the EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index, a value-based, multi-component metric framework for medical publications. Metric weighting and grouping were informed by a statistical analysis of 2891 Phase III clinical trial publications and by a panel of stakeholders who provided value assessments. The EMPIRE Index comprises three component scores (social, scholarly, and societal impact), each incorporating related altmetrics indicating a different aspect of engagement with the publication. These are averaged to provide a total impact score and benchmarked so that a score of 100 equals the mean scores of Phase III clinical trial publications in the New England Journal of Medicine (NEJM) in 2016. Predictor metrics are defined to estimate likely long-term impact. The social impact component correlated strongly with the Altmetric Attention Score and the scholarly impact component correlated modestly with CiteScore, with the societal impact component providing unique insights. Analysis of fresh metrics collected 1 year after the initial dataset, including an independent sample, showed that scholarly and societal impact scores continued to increase, whereas social impact scores did not. Analysis of NEJM 'notable articles' showed that observational studies had the highest total impact and component scores, except for societal impact, for which surgical studies had the highest score. The EMPIRE Index provides a richer assessment of publication value than standalone traditional and alternative metrics and may enable medical researchers to assess the impact of publications easily and to understand what characterizes impactful research.