Objective To establish the association between increased levels of D‐dimer and severity of pre‐eclampsia. Methods A nested, prospective cohort, analytical case–control study was conducted among women with pre‐eclampsia between March 2017 and March 2018. Inclusion criteria were age over 18 years, gestational age of more than 20 weeks, a single pregnancy with a living fetus, and a diagnosis of pre‐eclampsia. D‐dimer was measured by immunoturbidimetry at the time of diagnosis of pre‐eclampsia, applying cut‐off points adjusted for gestational age. Statistical analysis involved unconditional logistic regression for the association of elevated D‐dimer with severe pre‐eclampsia adjusted by confounding variables. Results There were 132 patients with pre‐eclampsia, of which 44 were classed as controls and 88 were classed as having severe pre‐eclampsia (case group). Cohort characteristics included: age between 18 and 45 years (mean 28.0 ± 6.3 years); presence of gestational hypertension (10.6%), chronic arterial hypertension (9.0%); and gestational diabetes (5.3%). In the case group, levels of D‐dimer were significantly higher than in controls (19.3% vs 2.3%, odds ratio [OR] 10.30, 95% confidence interval [CI] 1.32–80.14, P=0.004) as well as significant in the unconditional logistic regression model adjusted for maternal age, parity, gestational age, and comorbidities (OR 10.02, 95% CI 1.28–78.68, P=0.028). Conclusion Elevated levels of D‐dimer and severe pre‐eclampsia are strongly associated, reinforcing evidence that one of the physiopathologic bases of the condition is the activation of fibrinolysis and the coagulation system.