Objective: To perform a cost-effectiveness analysis of skin antiseptic solutions (chlorhexidine-alcohol (CHG) versus povidone iodine-alcohol solution (PVI)) for the prevention of intravascular-catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) in France based on an open-label, multicentre, randomised, controlled trial (CLEAN). Design: A 100-day time semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN database. This model includes eight health states and probabilistic sensitivity analyses on cost and effectiveness were performed. Costs of intensive care unit stay are based on a French multicentre study and the cost-effectiveness criterion is the cost per patient with catheter-related bloodstream infection avoided. Patients: 2,349 patients (age≥18 years) were analyzed to compare the 1-time CHG group (CHG-T1, 588 patients), the 4-time CHG group (CHG-T4, 580 patients), the 1-time PVI group (PVI-T1, 587 patients), and the 4-time PVI group (PVI-T4, 594 patients). Intervention: 2% chlorhexidine-70% isopropyl alcohol (chlorhexidine-alcohol) compared to 5% povidone iodine-69% ethanol (povidone iodine-alcohol). Results: The mean cost per alive, discharged or dead patient was of €23,798 (95% confidence interval: €20,584; €34,331), €21,822 (€18,635; €29,701), €24,874 (€21,011; €31,678), and €24,201 (€20,507; €29,136) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. The mean number of patients with CRBSI per 1000 patients was of 3.49 (0.42; 12.57), 6.82 (1.86; 17.38), 26.04 (14.64; 42.58), and 23.05 (12.32; 39.09) for CHG-T1, CHG-T4, PVI-T1, and PVI-T4, respectively. In comparison to the 1-time PVI solution, the 1-time CHG solution avoids 22.55 CRBSI /1,000 patients, and saves €1,076 per patient. This saving is not statistically significant at a 0.05 level because of the overlap of 95% confidence intervals for mean costs per patient in each group. Conversely, the difference in effectiveness between the CHG-T1 solution and the PVI-T1 solution is statistically significant. Conclusions: The CHG-T1 solution is more effective at the same cost than the PVI-T1 solution. CHG-T1, CHG-T4 and PVI-T4 solutions are statistically comparable for cost and effectiveness. This study is based on the data from the RCT from 11 French intensive care units registered with www.clinicaltrials.gov (NCT01629550).