Objective To investigate the factors affecting the incidence of epilepsy after cranioplasty.Methods A retrospective case control study was conducted on the clinical data of 171 patients with skull defect who underwent cranioplasty between January 2012 and December 2015.There were 126 males and 45 females,with an average age of 50.9 years (range,16-78 years).The patients were divided into epileptic seizure group (61 cases) and non epileptic seizure group (110 cases).The gender,age,defect cause,defect location,defect duration,perioperative antiepileptic drug use,skull defect regional depression volume (Vd),skull defect regional integrity volume (Vf),skull defect regional depression rate (Pd) of two groups were recorded.Univariate analysis and multivariate logistic regression analysis were used to identify the independent risk factor of epilepsy after cranioplasty.Results All patients were followed up for 54 months averagely (range,18-90 months).Sixty-one patients (35.7％) had epilepsy after cranioplasty.Univariate analysis suggested that age,defect cause,defect location,defect duration,perioperative antiepileptic drug use,and Vf were not associated with epilepsy after cranioplasty (all P ＞ 0.05);while gender,Vd,and Pd was associated with epilepsy after cranioplasty (P ＜ 0.05).Multivariate logistic regression analysis demonstrated that Pd (OR =0.024,95％ CI 0.001-0.502,P ＜0.05) was independent predictor of epilepsy after cranioplasty.Conclusion Pd is an independent risk factor for epilepsy after cranioplasty and depression degree could significantly affect its incidence.