Pseudomonas aeruginosa is the leading cause of pneumonia in intensive care units (ICUs), with multidrug-resistant (MDR) strains posing a serious threat. The aim of this study was to assess the clinical relevance of MDR Pseudomonas isolates in respiratory clinical specimens. A 5-year retrospective observational study in four medical-surgical ICUs from a referral hospital was carried out. Of 5667 adults admitted to the ICU, 69 had MDR-PA in respiratory samples: 31 were identified as having pneumonia (HAP/VAP): 21 ventilator-associated pneumonia (VAP) and ten hospital-acquired pneumonia (HAP). Twenty-one (67.7%) adults with MDR-PA HAP/VAP died after a median of 4 days (18 of the 21 deaths within 8 days), compared with one (2.6%) without pneumonia at day 8. In a Cox proportional regression model, MDR-PA pneumonia was an independent variable [adjusted hazard ratio (aHR) 5.92] associated with 30-day ICU mortality. Most strains (85.1%) were susceptible to amikacin and colistin. Resistance to beta-lactams (third-generation cephalosporins and piperacillin-tazobactam) ranged from 44.1% to 45.3%. Meropenem showed poor overall activity (MIC[50/90] 16/32 mg/dL), with 47.0% having a minimum inhibitory concentration (MIC) breakpoint >8 mg/L. Twenty-four (77.4%) HAP/VAP episodes received inappropriate empirical therapy. Although empirical combination therapy was associated with less inappropriate therapy than monotherapy (16.7% vs. 88.3%, p < 0.01), there was no difference in survival (30% vs. 33.3%, p = 0.8). Pneumonia was identified in one-third of adult ICU patients harbouring MDR-PA in respiratory clinical specimens. These patients have a 6-fold risk of (early) death compared to ventilator-associated tracheobronchitis (VAT) and respiratory colonisation. New antibiotics and adjuvant therapies are urgently needed to prevent and treat MDR-PA HAP/VAP.