Background Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI). Methods In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death. Results During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420-1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14-2.20, P = 0.007) and high (>= 1150 ng/mL, HR: 1.98, 95 % CI: 1.36-2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P (difference) = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P (difference) = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P (difference) < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %). Conclusions For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.