Background: Delirium is common in adult patients undergoing cardiac surgery and related to a high morbidity and mortality. Although a variety of pharmacologic interventions have been applied in delirium prevention, there is still uncertainty concerning which drug is optimal. Thus, we plan to conduct a systematic review and network meta-analysis (NMA) of published studies to assess the efficacy and safety of pharmacologic interventions for preventing delirium among those patients. Methods: A systematic literature search will be conducted in Embase, PubMed, and the Cochrane Library. The primary outcome will be the incidence of postoperative delirium. Secondary outcomes will include all-cause mortality and length of hospital or intensive care unit stay. A frequentist NMA will be conducted using Stata version 14.0. The inconsistency between direct and indirect comparisons will be evaluated using a node splitting method. In addition, surface under the cumulative ranking area will be used to evaluate superiority of different treatments. Results: The findings of our review will be submitted to a peer-reviewed publication. Conclusion: Our study will generate convincing evidence regarding the effectiveness and safety of different pharmacologic interventions for delirium prevention in cardiac surgery patients.