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Study Design: Multicenter, prospective, cohort study., Objective: To estimate the Minimal Clinically Important Difference (MCID) for the physical (PCS) and mental (MCS) component summaries of Short Form SF-12 (SF-12), in patients with low back pain (LBP)., Summary of Background Data: Quality of life is one of the core domains recommended to be assessed in patients with LBP. SF-12 is the most widely used instrument for this purpose, but its MCID was unknown., Methods: A total of 458 patients with subacute and chronic LBP were consecutively recruited across 21 practices. LBP, referred pain, disability, PCS, and MCS were assessed upon recruitment and 12 months later. Self-reported health status change between baseline and 12 month-assessment, was used as the external criterion. The MCID for SF-12 was estimated following four anchor-based methods; minimal detectable change (MDC); average change (AC); change difference (CD); and receiver operating characteristic curve (ROC), for which the area under the curve (AUC) was calculated. The effect on MCID values of pain duration and baseline scores was assessed., Results: Values for PCS were: MDC: 0.56, AC: 2.71, CD: 3.29, and ROC: 1.14. Values for MCS were: MDC: 3.77, AC: 3.54, CD: 1.13, and ROC: 4.23. AUC values were <0.7; MCID values were smaller among chronic patients and those with better baseline quality of life., Conclusion: Different methods for MCID calculation lead to different results. In patients with subacute and chronic LBP, improvements >3.77 in MCS and >3.29 in PCS, can be considered clinically relevant. MCID is smaller in patients with longer pain duration and better baseline quality of life., Level of Evidence: 2.