Purpose <p>This study provides an economic evaluation of bedside, data-driven, and model-informed precision dosing of antibiotics in comparison with usual care among critically ill patients with sepsis or septic shock.</p> Methods <p>This economic evaluation was conducted alongside an AutoKinetics randomized controlled trial. Effect measures included quality-adjusted life years (QALYs), mortality and pharmacokinetic target attainment. Costs were measured from a societal perspective. Missing data was multiply imputed, and bootstrapping was used to estimate statistical uncertainty. Differences in effects and costs were estimated using bivariate regression and used to calculate incremental cost-effectiveness ratios.</p> Results <p>Patients in the intervention group had higher costs (€42,684 vs. 39,475), lower mortality (42% vs. 49%), more QALYs (0.184 vs. 0.153), and higher pharmacokinetic target attainment (69% vs. 48%). Only the difference for target attainment was found statistically significant. An additional €18,129, €55,576, and €123,493 needs to be invested to attain the targeted plasma levels for one more patient, to save one life and gain one QALY, respectively. The probability of cost-effectiveness for all effect outcomes is below 60% for most acceptable willingness-to-pay thresholds.</p> Conclusions <p>Data-driven personalised antibiotic dosing in critically ill patients as implemented in the AutoKinetics trial cannot be recommended for implementation as a cost-effective intervention.</p> Trial registration <p>The trial was prospectively registered at Netherlands Trial Register (NTR), NL6501/NTR6689 on 25 August 2017 and at the European Clinical Trials Database (EudraCT), 2017-002478-37 on 6 November 2017.</p>