A total number of 339 patients who received a pacemaker implantation between June 2012 and June 2014 at Tongji Hospital of Tongji Medical College (Wuhan, China) were investigated in the present study. The aims of the present study were to explore the risk factors of pocket hematoma following pacemaker implantation, and to analyze the effect of anti-allergy treatment on pocket-related complications following pacemaker implantation. Predictors of hematoma occurrence were determined and analyzed via a Chi-square test. Patients suffering from pocket hematoma, which were indicated to be partially caused by an allergic reaction to the pacemaker component, were distinguished by routine blood parameters. Furthermore, the pacemaker component was distinguished by histopathological examinations in one patient. Promethazine (25 mg/day) was used to treat allergic patients. The results demonstrated that in patients with a history of allergies, the rate of pocket hematoma was significantly higher when compared with patients without a history of allergies (22.00 vs. 7.61%; P=0.027). A significantly increased incidence of hematoma was indicated in patients with a lower body mass index when compared with patients of normal weight (15.79 vs. 7.38%; P=0.042). Furthermore, implantation of larger-sized devices, such as an implantable cardioverter-defibrillator and cardiac resynchronization therapy, were significantly predictive of hematoma development (29.63 vs. 8.01%; P=0.015). Patients with diabetes were also identified to exhibit a significantly high incidence of hematoma (22.22 vs. 8.25%; P=0.023). Promethazine administration significantly decreased the incidence of re-operating (P=0.017) and the duration of hospital stay (P=0.038) in patients whose pocket hematoma was caused by an allergy. In conclusion, promethazine may be a beneficial agent to treat pocket hematoma caused by allergic reactions following pacemaker surgery.