The aim of the study was to simplify the first Sigma erythrocyte sedimentation rate (ESR) method (manual hematocrit adjustment to 0.35, sum of 4 sedimentation levels) and to confirm its clinical relevance. The erythrocyte sedimentation rate of undiluted blood samples from 576 patients was measured simultaneously with and without manual hematocrit adjustment to 0.35 to identify an approximate expression of the area under the curve and a formula for calculating the Sigma ESR. The Sigma ESR formula was based on the sum of 2 unadjusted sedimentation levels, at 30 and 60 minutes, together with the hematocrit value and the hemoglobin concentration. Sigma ESR values in 274 healthy subjects showed a gaussian distribution, no difference between men and women, and no significant increase with age. In recent-onset arthritis or disk-related lumbosciatic syndrome, Sigma ESR seemed to be a more reliable marker of inflammation than the Westergren ESR and C-reactive protein. We also obtained data clarifying the controversial relationship of ESR with lipid levels and arterial hypertension.