Background The relationships between coagulation factors and non-small cell lung cancer (NSCLC) prognosis have been intensively studied. However, no previous study has investigated the combined effects of preoperative platelet (PLT), fibrinogen (FIB), and D-dimer (D-D) levels on the prognosis of NSCLC. Methods A multicenter prospective study was conducted over seven hospitals. A total of 395 patients diagnosed with operable NSCLC for the first time were included and followed-up until disease progression or the end of the study. Baseline demographic and clinicopathological information, and preoperative coagulation test results were collected for each patient. Univariate and multilevel survival analyses were conducted using Cox regression and shared frailty models. Results Multilevel analyses revealed that there was a marginally significant association between elevated PLT level (> 215 x 10(9)/L) and unfavorable progression-free survival (PFS) (hazard ratio 2.42, P = 0.05), whereas preoperative FIB and D-D were not significant prognostic factors for PFS (P = 0.31 and 0.30, respectively). Compared to patients with one elevation of the three coagulation factors, patients with at least two elevations of the three factors had a significantly higher risk of cancer progression (hazard ratio 4.62, P = 0.02). Conclusion The number of elevated preoperative coagulation factors may have a significant effect on PFS and could be used to predict the prognosis of NSCLC patients after surgery. Future studies are warranted to further investigate the interactions between these three coagulation factors.