Our aim was to determine serum concentrations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its decoy receptor osteoprotegerin (OPG) in patients with mild and moderate to severe acute pancreatitis (AP) in the early phase of the disease.We included 40 patients with AP (16 women, 24 men) admitted to Ist Department of Surgery, Jagiellonian University Medical College, Krakow. Twenty-eight had mild (MAP) and twelve moderate to severe form of AP (SAP). Serum concentrations of OPG and TRAIL were measured by ELISA at admission and on days 3, 5 and 7.Both TRAIL and OPG were elevated in AP patients as compared to reference values. Starting from day 3 of the study, OPG concentrations were significantly higher in SAP than in MAP. Also, day 3 OPG was higher in patients who died from AP. OPG positively correlated with Glasgow score, C-reactive protein (CRP) concentrations and length of hospital stay. Day 3 OPG cut-off of 713 pg/mL enabled to differentiate between SAP and MAP with sensitivity of 71% and specificity of 80%. Area under ROC curve was 0.795, comparable to that achieved for CRP (0.838; p >0.05). In contrast, serum concentrations of TRAIL were not associated with AP severity.Determination of serum OPG concentrations may help in early prediction of severity of AP. However, diagnostic utility of the measurements seems too low to use OPG as a single clinically reliable predictor. Serum TRAIL is not useful in the differentiation between mild and severe form of AP.