This article is second translation of a GRADE series published in the BMJ to create a highly structured, transparent, and informative system for rating quality of evi-dence for developing recommendations. The process to develop a guideline, we should formulate a clear question with specification of all outcomes of importance to patients. Grading of Recommendations, Assessment, Development and Evaluation(GRADE) offers four levels of evidence quality: high, moderate, low, and very low for these patient-important outcomes. Randomized trials begin as high quality evidence and observational studies as low quality evidence. Although randomized trials begin as high quality evidence, quality may be downgraded as a result of study limitations (risk of bias), inconsistency (variability in results), indirectness, impre-cision (wide confidence intervals), or publication bias. While the quality of evidence derived from observational studies starts at ‘low’ but may be upgraded based on a very large magnitude of effect, a dose-response gradient, and if all plausible biases would reduce an apparent treatment effect.