OBJECTIVE Decreased level of serum calcium was commonly seen in critical illness. Hypocalcemia was significantly more frequent in patients with severe form of acute pancreatitis (AP), and a negative correlation was observed between endotoxemia and serum calcium in AP. AP patients with persistent organ failure (POF) show an extremely high mortality. The association underlying calcium and POF in AP has not been characterized. METHODS We conducted a retrospective cohort study of adult patients who presented within 72hours from symptom onset of AP at our center between January 2014 and May 2015. Demographic parameters on admission, organ failure assessment, laboratory data and in-hospital mortality were compared between patients with and without POF. Uni-and multi-variate logistic regression analyses were utilized to evaluated the predictive ability of serum calcium. RESULTS A total of 128 consecutive AP patients, including 29 with POF, were included. Compared to patients without POF, patients with POF showed a significantly lower value of serum calcium on admission (2.11±0.46 vs. 1.55±0.36mmol/L, P<0.001). After multivariate logistic analysis, serum calcium remained an independent risk factor for POF (Hazard ratio 0.21, 95% confident interval: 0.08-0.58; P=0.002). A calcium value of 1.97mmol/L predicted POF with an area under the curve (AUC) of 0.888, a sensitivity with 89.7% and specificity with 74.8%, respectively. CONCLUSIONS Our results indicate that serum calcium on admission is independently associated with POF in AP and may serve as a potential prognostic factor.