Objective To investigate the feasibility of negative-pressure wound therapy (NPWT) in the treatment of uncomplicated cardiac pacemaker pocket infection. Methods From January 2013 to March 2020, 35 patients with uncomplicated cardiac pacemaker pocket infection were admitted to the Department of Cardiology of Peking University First Hospital, including 21 males and 14 females, aged 27 to 84 years. The retrospective cohort study was conducted. After a complete debridement followed by continuous NPWT (with negative pressure of -16.67 kPa), the pulse-generator was inserted into the new pocket between the musculus pectoralis major and pectoralis minor. Pressure drainage tube was put into the old pocket space. NPWT with the same mode was used again for 5 to 7 days after the wound was closed. The removed pocket tissue of patients was observed with hematoxylin-eosin staining. The wound healing on 10 to 12 days after the operation of pacemaker replacement was observed, and the recurrence of infection was observed during 6 to 42 months follow-up after operation. Results The fibrous sac wall was observed in pocket tissue of the patients, and the tissue was partially covered with stratified epithelium, with many chronic inflammatory cells infiltration. Multinucleated giant cell reaction was observed in the tissue of some patients. Ten to twelve days after the operation of pacemaker replacement, 35 patients had good wound healing, and sutures were removed. After 6 to 42 months follow-up after operation, 31 patients were cured with no recurrence of infection and the wounds were well-healed; 4 patients who had recurrent infection received whole system of pacemaker removal after the operation. Conclusions On the premise of complete debridement, NPWT is an alternative treatment for patients with uncomplicated cardiac pacemaker pocket infection.