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OBJECTIVES . The aim of the present meta-analysis was to compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections. DATA SOURCES MEDLINE, Google Scholar and the Cochrane Library STUDY ELIGIBILITY CRITERIA AND INTERVENTIONS: . Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used in monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or Hospital-Acquired or Ventilator-Associated Pneumonia (HAP/VAP) due to P. aeruginosa. The outcomes evaluated were hospital-mortality, 14-day- or 30-day-mortality rate, microbiological eradication rate and clinical cure rate. RESULTS . Of a total of 8,363 citations screened, 6 Randomized Controlled Trials (RCTs), 6 prospective cohort studies, and 21 retrospective cohort studies were included in the analysis, accounting for a total of 3,861 subjects. Considering the 14 studies evaluating the empirical therapy, no significant difference in mortality rate was observed between the two groups (RR: 1.06; 95% CI 0.86-1.30, p=0.6). Similar findings were obtained among the 18 studies analysing the targeted therapy (RR: 1.04; 95% CI 0.83-1.31, p=0.708); however, grouping the studies according to the design, a higher mortality among patients receiving monotherapy was observed in 5 prospective studies (RR: 1.37; 95% CI 1.06-1.79, p=0.018). Finally, no difference was observed among groups considering the microbiological and the clinical cure. CONCLUSIONS . Our meta-analysis demonstrated no difference in the mortality rate, clinical cure and microbiological cure in patients treated with beta-lactam monotherapy or combination for P. aeruginosa infections.