Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) continues to be a major contributor to morbidity after pancreaticoduodenectomy (PD), but it remains unclear what risk factors can precisely predict the development of CR-POPF after laparoscopic pancreatoduodenectomy (LPD). We thus aimed to identify the risk factors for predicting CR-POPF after LPD. Methods: A total of 388 consecutive patients who underwent LPD at our institution between July 2014 and December 2018 were identified. All data, including pre-, intra-, and postoperative risk factors associated with CR-POPF defined by the International Study Group of Pancreatic Fistula, were collected retrospectively. To evaluate the predictive performance of the risk factor models, areas under the receiver operating characteristic curve (ROC) were determined. Results: CR-POPF was observed in 31 patients (8.0%) with significant association observed with body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA), intra-abdominal fat thickness, main pancreatic duct width, soft pancreatic texture, operative time, underlying pathology, and albumin (Alb) on postoperative days (POD) 1-3. Multivariate analyses revealed that VFA >82 cm(2) [odds ratio (OR)=11.088; P=0.029], main pancreatic duct width <3 mm (OR=7.701; P=0.001), soft pancreatic texture (OR=12.543; P=0.022), and operative time >320 min (OR=6.061; P<0.001) were independent risk factors for CR-POPF after LPD. Areas under the ROC curve (AUC) analysis revealed the pancreatic texture was the strongest single predictor (AUC=0.854) of CR-POPF, and pancreatic texture + pancreatic duct width was the best two-predictor model (AUC=0.904). Meanwhile, our findings indicated an association between the TFA >221 cm(2) (OR=8.637; P=0.001) and VFA >82 cm(2) (OR=7.009; P<0.001) with soft pancreatic texture. Conclusions: Soft pancreatic texture, VFA >82 cm(2), main pancreatic duct width <3 mm, and operative time >320 min were independent predictive risk factors of CR-POPF for LPD.