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Background: Delirium is one of the most common complications of hospitalisation in geriatric patients. One of the highest incidences of postoperative delirium (POD) is found among the elderly population undergoing orthopaedic surgery. Given that delirium can lead to many negative outcomes, there is a growing need to find and implement evidence-based interventions to prevent POD. Aim: This review aims to determine which interventions may prevent the development of POD in geriatric patients undergoing orthopaedic surgery. Design: A systematic literature review was performed. Methods: To review the effectiveness of various pharmacological and non-pharmacological interventions in the prevention of postoperative delirium in orthopaedic geriatric patients (>65 years), a systematic review was performed. A search was applied to the Embase and Cochrane central database. The search was restricted to randomised controlled trials, systematic reviews, and meta-analyses. Results: Out of 400 initial results, 13 articles were retrieved, with a total of 2077 patients included. Findings were categorised based on the action mechanism of the interventions. The studies showed that interventions such as the use of melatonin, music, a delirium prevention care protocol, hypertonic saline, blood pressure manipulation, and the use of a rivastigmine patch may significantly lower the incidence of POD. However, the use of haloperidol, dexamethasone, ramelteon and the combination of transcutaneous electrical acupoint with an integrated perioperative nursing program, did not have a significant effect on the incidence of POD in these studies. Conclusions: Different pharmacological and non-pharmacological interventions, such as the use of melatonin, music, a delirium prevention care protocol, hypertonic saline, intraoperative blood pressure management, and the use of a rivastigmine patch displayed a significant effect on decreasing the incidence of POD. However, more evidence is necessary to be able to generalise these findings. Larger studies specifically within the elderly orthopaedic surgical population are thus needed. Additionally, considering the complex pathophysiology of delirium, more research should focus on multi-interventional protocols as they present promising results. Relevance for practice: Based on today’s evidence, the use of melatonin, haloperidol, and a delirium prevention care protocol, could be considered to prevent delirium in clinical practice. For other interventions, more extensive and high-quality research is necessary before being able to implement them in daily clinical practice.