Abstract Background The prognostic nutritional index (PNI) and D-dimer (DD) levels represent useful prognostic indicators in colorectal cancer (CRC); however, a combination of these indicators, namely, the PNI and DD score (PDS) was less addressed. Methods A retrospective study with 183 patients after curative surgery was conducted. Patients were divided into 3 subgroups: PDS 0, decreased PNI and increased DD levels; PDS 1, decreased or increased PNI and DD levels; PDS 2, increased PNI and decreased DD levels. The differences in disease-free survival (DFS) and overall survival (OS) were compared among these subgroups, and risk factors for outcome were determined. Results A total of 56, 65 and 62 patients were assigned to the PDS 0, 1 and 2 subgroups, respectively. PDS was significant in predicting both the DFS (area under the curve (AUC) = 0.68, P