Purpose <p>Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) has been classified by the World Health Organization as one of the most alarming antimicrobial-resistant microorganisms. Despite the availability of newer therapeutic options, polymyxins remain important last-resort agents for the treatment of CRPA infections in many settings. With the extended use of polymyxins in the treatment of extensively drug-resistant bacterial infections, both colistin resistance rates, colistin heteroresistance (CHR) rates and antibiotic treatment failures have risen. In this study, we aimed to: (i) determine the prevalence of CHR in <i>P. aeruginosa</i> bloodstream isolates, (ii) compare the accuracy of the antibiotic gradient test (GT) with the population analysis profiling (PAP) method, and (iii) identify clinical risk factors for CHR.</p> Methods <p>CHR was investigated among 70 colistin-susceptible <i>P. aeruginosa</i> strains isolated from blood cultures using PAP and GT methods. Clinical and demographical data were retrospectively reviewed, and risk factors for CHR were analyzed using logistic regression.</p> Results <p>We detected a remarkably high prevalence of CHR (61.4%) among colistin-susceptible <i>P. aeruginosa</i> bloodstream isolates. The gradient test failed to detect any of the heteroresistant strains. Our analysis revealed that age ≥ 60 years, lack of recent hospitalization, and a colistin MIC of 1&#xa0;mg/L, compared with 2&#xa0;mg/L, were independently associated with an increased risk of CHR. CHR was not significantly associated with 30-day or 90-day mortality.</p> Conclusion <p>Despite the microbiological importance of heteroresistance, the clinical impacts and underlying mechanisms of this phenotype remain to be elucidated.</p>