•Ceftazidime-avibactam (CAZ-AVI) is an effective and safe therapy for multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa infections•It is especially useful for strains with class A carbapenemase production•Early therapy with CAZ-AVI is associated with better outcomes•CAZ-AVI as part of combination therapy provides no clear benefits over monotherapy Clinical experience with ceftazidime-avibactam (CAZ-AVI) for treatment of infections due to multidrug or extremely resistant (MDR/XDR) Pseudomonas aeruginosa (P. aeruginosa) is limited. A retrospective cohort study was conducted on patients with MDR/XDR P. aeruginosa infections treated with CAZ-AVI. The primary outcome was clinical cure by day 14, evaluated by logistic regression adjusted for the propensity score to receive CAZ-AVI as combination therapy. Secondary outcomes were 30-day all-cause mortality, 90-day recurrence, emerging CAZ-AVI resistance, and safety of therapy. Sixty-one first episodes of MDR/XDR P. aeruginosa infection were included. The most common source was lower respiratory tract infection (34.4%), 14.8% episodes developed bloodstream infection and 50.8% had sepsis at presentation. Ceftazidime-avibactam therapy was initiated at a median of 7.0 (interquartile range IQR: 3.5-12.0) days from symptom onset; it was used as combined therapy in 29 (47.5%) episodes. Clinical cure rate by day 14 was 54.1% and predictors of response were days to source control (adjusted odds ratio aOR: 0.84; 95% confidence interval CI: 0.72-0.98; P = 0.024), days until the initiation of CAZ-AVI therapy (aOR: 0.65; 95% CI: 0.49-0.86; P = 0.003), age (aOR: 1.07; 95% CI: 0.99-1.15; P = 0.066) and CAZ-AVI combination therapy (aOR: 0.02; 95% CI: 0.01-0.38; P = 0.009). Rates of 30-day all-cause mortality and 90-day recurrence were 13.1% and 12.5%, respectively. Emergence of drug resistance to CAZ-AVI was not detected. Treatment-related adverse events occurred in three episodes (4.9%). CAZ-AVI constitutes a valid alternative for the treatment of infections due to MDR/XDR P. aeruginosa.