Purpose Postoperative pancreatic fistula (POPF) is a complication discussed in the context of pancreatic surgery, but may also result from splenectomy; a relationship that has not been investigated extensively yet. Methods This retrospective single-center study aimed to analyze incidence of and risk factors for POPF after splenectomy. Patient characteristics included demographic data, surgical procedure, and intra- and postoperative complications. POPF was defined according to the International Study Group on Pancreatic Surgery as POPF of grade B and C or biochemical leak (BL). Results Over ten years, 247 patients were identified, of whom 163 underwent primary (spleen-associated pathologies) and 84 secondary (extrasplenic oncological or technical reasons) splenectomy. Thirty-six patients (14.6%) developed POPF of grade B/C or BL, of which 13 occurred after primary (7.9%) and 23 after secondary splenectomy (27.3%). Of these, 25 (69.4%) were BL, 7 (19.4%) POPF of grade B and 4 (11.1%) POPF of grade C. BL were treated conservatively while three patients with POPF of grade B required interventional procedures and 4 with POPF of grade C required surgery. POPF and BL was noted significantly more often after secondary splenectomy and longer procedures. Multivariate analysis confirmed secondary splenectomy and use of energy-based devices as independent risk factors for development of POPF/BL after splenectomy. Conclusion With an incidence of 4.5%, POPF is a relevant complication after splenectomy. The main risk factor identified was secondary splenectomy. Although POPF and BL can usually be treated conservatively, it should be emphasized when obtaining patients’ informed consent and treated at centers with experience in pancreatic surgery.