This study investigated the changes in antibiotic resistance in recurrent Pseudomonas aeruginosa infections in chronic suppurative otitis media (CSOM). Its aim was to provide a treatment strategy for P aeruginosa infections in CSOM for the prevention of multidrug resistance. A case-control study was conducted in tertiary teaching hospitals in Korea. The experimental group included patients with recurrent P aeruginosa infection who had relapsed within 2 months after the successful control of a previous P aeruginosa infection. The control group consisted of patients with a P aeruginosa infection who had no history of such an infection. An antibiotic sensitivity test was performed for each culture. The proportion of recurrent P aeruginosa infection was 22.69% (98 of 432 cases). Drug resistance to amikacin, tobramycin, netilmicin, ciprofloxacin, and levofloxacin was significantly changed after recurrent infection. The fluoroquinolone strains seen in recurrent P aeruginosa showed high cross-resistance to other drugs. Antibiotic resistance of P aeruginosa in CSOM changed with recurrent infection.