Objective.To test the OMERACT 8 draft validation criteria for soluble biomarkers by assessing the strength of literature evidence in support of 5 candidate biomarkers.Methods.A systematic literature search was conducted on the 5 soluble biomarkers RANKL, osteoprotegerin (OPG), matrix metalloprotease (MMP-3), urine C-telopeptide of types I and II collagen (U-CTX-I and U CTX-II), focusing on the 14 OMERACT 8 criteria. Two electronic voting exercises were conducted to address: (1) strength of evidence for each biomarker as reflecting structural damage according to each individual criterion and the importance of each individual criterion; (2) overall strength of evidence in support of each of the 5 candidate biomarkers as reflecting structural damage endpoints in rheumatoid arthritis (RA) and identification of omissions to the criteria set.Results.The search identified 111 articles. The strength of evidence in support of these biomarkers reflecting structural damage was low for all biomarkers and was rated highest for U-CTX-II [score of 6.5 (numerical rating scale 0–10)]. The lowest scores for retention of specific criteria in the draft set went to criteria that refer to the importance of animal studies, correlations with other biomarkers reflecting damage, and an understanding of the metabolism of the biomarker.Conclusion.Evidence in support of any of the 5 tested biomarkers (MMP-3, CTX-I, CTX-II, OPG, RANKL) was inadequate to allow their substitution for radiographic endpoints in RA. Three of the criteria in the draft criteria set might not be required, but few omissions were identified.