This study aimed to determine the incidence of maxillary sinus pathology in patients with a midfacial fracture who underwent osteosynthesis surgery and evaluate the associated risk factors. We conducted a retrospective case-control analysis of patients with midfacial fractures involving a maxillary sinus wall who were treated with open reduction and internal fixation (ORIF) between January 2015 and December 2020. Fracture reduction, the number of screws implanted in the maxillary sinus, and the number of screws penetrating the maxillary sinus, etc., were examined as potential risk factors. Maxillary sinus pathology on postoperative CT was considered the primary outcome for case-control analysis. Binary logistic regression was used to identify variables associated with postoperative maxillary sinus pathology. Thereafter, propensity score matching (PSM) was used to extract confounding factors. A total of 262 patients (totaling 372 maxillary sinuses) were included for analysis. PSM yielded 178, 246, and 70 matched sinuses, respectively, depending on the potential risk factors. Postoperative maxillary sinus pathology was visualized in 218 of the 372 maxillary sinuses (58.60%). The risk factors for postoperative maxillary sinus pathology included the number of screws penetrating the maxillary sinus (odds ratio (OR), 1.124; p = 0.007), an imperfect maxillary sinus wall fracture reduction (OR, 2.901; p = 0.021), and the number of sinus walls involved (OR, 1.383; p = 0.011). After PSM, postoperative maxillary sinus pathology was still more prevalent in sinuses with multiple maxillary sinus wall fractures (64.04% vs. 48.31%, p = 0.034), sinuses with more screws penetrating the maxillary sinus (64.23% vs. 50.41%, p = 0.028), and sinuses with an imperfect reduction (80% vs. 51.43%, p = 0.012). In conclusion, maxillary sinus pathology is common after the ORIF of midfacial fractures. Patients with a fracture of multiple maxillary sinus walls require a close follow-up. Screw penetration of the maxillary sinus should be avoided to prevent maxillary sinus pathology after a midfacial fracture ORIF.