The erythrocyte sedimentation rate (ESR) can be used to identify low-grade inflammation that contributes to future vascular events. ESR determinants, however, have not been explored in the absence of a subclinical or microinflammatory response. The ESR was determined in a large cohort of apparently healthy participants, excluding subjects with high-sensitivity C-reactive protein (hs-CRP) concentrations more than 5 mg/L (47.62 nmol/L). Linear regression models were used to identify the determinants of the ESR. The study population comprised 6,237 subjects. The main laboratory variables found to affect ESR were levels of fibrinogen, hemoglobin, globulin, and triglycerides (all P < .001; R2 = 0.34 and 0.44 for men and women, respectively). Sex was found to affect ESR alone and in combined interactions with most other variables. Age did not affect ESR. The main determinants of ESR in an inflammation-free cohort are sex and levels of fibrinogen, hemoglobin, globulins, and triglycerides.