Abstract: Purpose: To compare the effects of prevention interventions on delirium occurrence in critically ill adults. Methods: MEDLINE, Embase, PsychINFO, CINAHL, Web of Science, Cochrane Library, Prospero, and WHO international clin. trial registry were searched from inception to Apr. 8, 2021. Randomized controlled trials of pharmacol., sedation, non-pharmacol., and multi-component interventions enrolling adult critically ill patients were included. We performed conventional pairwise meta-analyses, NMA within Bayesian random effects modeling, and determined surface under the cumulative ranking curve values and mean rank. Reviewer pairs independently extracted data, assessed bias using Cochrane Risk of Bias tool and evidence certainty with GRADE. The primary outcome was delirium occurrence; secondary outcomes were durations of delirium and mech. ventilation, length of stay, mortality, and adverse effects. Results: Eighty trials met eligibility criteria: 67.5% pharmacol., 31.3% non-pharmacol. and 1.2% mixed pharmacol. and non-pharmacol. interventions. For delirium occurrence, 11 pharmacol. interventions (38 trials, N = 11,993) connected to the evidence network. Compared to placebo, only dexmedetomidine (21/22 alpha2 agonist trials were dexmedetomidine) probably reduces delirium occurrence (odds ratio (OR) 0.43, 95% Credible Interval (CrI) 0.21-0.85; moderate certainty). Compared to benzodiazepines, dexmedetomidine (OR 0.21, 95% CrI 0.08-0.51; low certainty), sedation interruption (OR 0.21, 95% CrI 0.06-0.69; very low certainty), opioid plus benzodiazepine (OR 0.27, 95% CrI 0.10-0.76; very low certainty), and protocolized sedation (OR 0.27, 95% CrI 0.09-0.80; very low certainty) may reduce delirium occurrence but the evidence is very uncertain. Dexmedetomidine probably reduces ICU length of stay compared to placebo (Ratio of Means (RoM) 0.78, CrI 0.64-0.95; moderate certainty) and compared to antipsychotics (RoM 0.76, CrI 0.61-0.98; low certainty). Sedative interruption, protocolized sedation and opioids may reduce hospital length of stay compared to placebo, but the evidence is very uncertain. No intervention influenced mech. ventilation duration, mortality, or arrhythmia. Single and multi-component non-pharmacol. interventions did not connect to any evidence networks to allow for ranking and comparisons as planned; pairwise comparisons did not detect differences compared to standard care. Conclusion: Compared to placebo and benzodiazepines, we found dexmedetomidine likely reduced the occurrence of delirium in critically ill adults. Compared to benzodiazepines, sedation-minimization strategies may also reduce delirium occurrence, but the evidence is uncertain.