Pregnancy-associated plasma protein A (PAPP-A) is a new prognostic indicator of acute coronary syndrome. This protein is elevated in hemodialysis (HD) patients and is closely related to inflammation and oxidative stress. The aim of our pilot study was to find out whether PAPP-A is related to mortality in HD patients. 40 HD patients in a stable clinical state (20 men and 20 women, mean age 69 ± 12 years) were enrolled in the study and followed up for 20 months. PAPP-A was assessed immunochemically (TRACE method) in serum samples (before the HD session) at the beginning of the observation period. During the follow-up, 22 patients died, 15 of them due to cardiovascular events. PAPP-A levels were significantly higher in the patients who died, compared to living HD patients: 26.8 (21.6–36.8) vs. 20 (14.9–26.6) mU/l, p = 0.034. PAPP-A could also be a new prognostic marker in hemodialysis patients, probably due to its close association with cardiovascular risk. More extensive studies are required to confirm this hypothesis.