Background: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to reporting quality of evidence and strength of recommendations appears discordant when the certainty in the balance of benefits and harms differs from the certainty of evidence for effect estimates.

Objectives: To frame conceptual development for defining Certainty of Net Benefit as a means to report the certainty that benefits outweigh harms.

Methods: Iterative refinement of ideas using input from workshops, presentations, and numerous large-group and small-group discussions.

Results: Certainty of net benefit is the confidence that the balance of benefits and harms is favourable. Determination of certainty of net benefit combines determination of certainty of effect estimates, importance of outcomes, and the combination of these concepts. Certainty of net harm is the confidence that the balance is unfavourable. Although the certainty of net benefit or harm may more closely align with the strength of recommendation, guideline panels may differ in direction or strength of recommendation when a favourable threshold is influenced by cost, acceptability, feasibility or equity.

Conclusions: Reporting the certainty of net benefit offers a way to express the certainty that benefits outweigh harms for a recommendation, and this can be an alternative way to characterise the trustworthiness of evidence supporting a recommendation.