IntroductionD-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker.MethodsThis multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis.ResultsThe study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51–2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02–4.54,P=0.044) and (OR: 4.74; 95% CI: 2.38–9.46,P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06–8.86,P<0.001).Conclusion:Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.