Background: Pseudomonas aeruginosa (P. aeruginosa) is one of the most common pathogens in hospital-acquired pneumonia (HAP) including ventilator-associated pneumonia (VAP). Recently, ceftolozane/tazobactam (CTLZ/TAZ) has been used to treat pneumonia due to P. aeruginosa. Case series: Two cases of P. aeruginosa pneumonia treated by CTLZ/TAZ that had been initially treated by piperacillin/tazobactam (PIPC/TAZ) are presented. (Case 1): A 76-year-old man who underwent esophagectomy developed severe pneumonia caused by P. aeruginosa infection and received oxygen by high-flow nasal canula. PIPC/TAZ was started, and he improved 10 days later. PIPC/TAZ was switched to sulbactam/ampicillin, but on day 14, his respiratory condition worsened, and septic shock developed. P. aeruginosa was isolated from his blood, and CTLZ/TAZ was started because the isolated P. aeruginosa showed resistance to PIPC/TAZ. Although he recovered on Day 28, and CTLZ/TAZ was switched to levofloxacin, his condition worsened again, and P. aeruginosa resistant to CTLZ/TAZ was isolated from his blood on day 32. Finally, he died of septicemia and renal failure. (Case 2) A 51-year-old woman who underwent surgery for a brain tumor developed VAP due to P. aeruginosa and was treated by PIPC/TAZ. Her pneumonia improved, but pneumothorax developed, and she was therefore switched to CTLZ/TAZ on day 7. Her pneumonia improved smoothly without bacteremia 10 days later. Conclusions: These data and cases suggest that CTLZ/TAZ was effective for severe P. aeruginosa pneumonia although the isolated P. aeruginosa was resistant to PIPC/TAZ. However, the duration of CTLZ/TAZ administration may need to be considered for pneumonia cases with bacteremia due to P. aeruginosa.