Aseptic bone flap resorption (BFR) is a known long-term complication after cranioplasty (CP). We analyzed our institutional data in order to identify risk factors for BFR. From October 1999 to April 2012, 254 patients underwent CP after decompressive craniectomy (DC) at our institution, and had a long-term follow-up period of >1 year after CP (range 12-146 months). Overall, BFR occurred in 10 of 254 patients as a long-term complication after CP (4%). BFR developed more often in patients aged ≤18 years (p=0.008), in patients who previously underwent DC for traumatic brain injury (p=0.04), and in patients with multiple fractures within the reinserted bone flap (p=0.002). Furthermore, BFR developed significantly more often in patients who underwent cranioplasty ≤2 months after DC (p=0.008), as well as in patients with wound healing disturbance or abscess as an early complication after the CP procedure (p=0.01). The multivariate analysis of the present data identified the presence of multiple fractures within the bone flap (p=0.002, OR 10.3, 95% CI 2.4-43.8), wound infection after CP (p=0.003, OR 12.3, 95% CI 2.3-65.3), and cranioplasty performed ≤2 months after DC (p=0.01, OR 6.3, 95% CI 1.5-26.3) as independent risk factors for the development of BFR after CP in a large series with long-term follow-up. This might influence future surgical decision making, especially in patients fulfilling high risk criteria for developing BFR.