Poor sleep quality is a common complaint after total joint arthroplasty (TJA), and it is associated with reports of higher pain and worse functional outcomes. Several interventions have been investigated with the intent to reduce the incidence of postoperative sleep disturbance with varying effectiveness. An aggregate of the best available evidence, along with an evaluation of the quality of those studies, is needed to provide valuable perspective to physicians and to direct future research. In this systematic review, we asked: (1) What is the reported efficacy of the most commonly studied medications and nonpharmacologic approaches, and (2) what are their side effects and reported complications? This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search using a combination of controlled vocabulary and keywords was performed utilizing Medline (Ovid), Embase (Ovid), Cochrane Central, and Web of Science databases from database inception to 2023, with the last search occurring October 24, 2023, to identify studies that evaluated a sleep intervention on the effect of patient-reported sleep quality after THA or TKA. Inclusion criteria were clinical trials, comparative studies, and observational studies on adult patients who underwent primary TKA or THA for osteoarthritis and who completed validated sleep questionnaires to assess sleep quality postoperatively. We excluded studies on patients younger than 18 years, patients with sleep apnea, TKA or THA because of trauma or conditions other than osteoarthritis, revision TJA, studies in languages other than English, and studies from nonindexed journals or preprint servers. Two investigators independently screened 1535 studies for inclusion and exclusion criteria and extracted data from the included studies. Ultimately, 14 studies were included in this systematic review, including 12 randomized controlled trials and 2 prospective comparative studies. A total of 2469 participants were included, with a mean ± SD age of 65 ± 7 years and 38% men in control groups and 65 ± 7 years and 39% men in intervention groups. Sleep quality questionnaires utilized included the Pittsburgh Sleep Quality Index, Self-Rating Scale of Sleep, 100-mm VAS - Sleep, Sleep Disturbance Numeric Rating Scale, Likert scales, and one institutionally designed questionnaire. Quality analysis was performed utilizing the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Randomized Controlled Trials, where higher scores of 13 indicated a more reliable study, and the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies, where higher scores of 9 indicated a more reliable study and scores < 5 represented a high risk of bias. Two of the randomized controlled trials scored a 12 of 13, and the remaining 10 met every criteria of the JBI checklist. Both comparative studies scored 5 of 9 possible points of the Newcastle-Ottawa Scale. Melatonin and selective cyclooxygenase-2 inhibitor rofecoxib were found to provide a clinically important benefit to sleep quality within the first postoperative week after TJA. However, rofecoxib was withdrawn from the market globally in 2004 over concerns about increased risk of cardiovascular events. Another cyclooxygenase-2 inhibitor, celecoxib, remains available. No other intervention demonstrated a clinical benefit. Side effects of melatonin include dizziness, headache, paresthesia, and nausea, and it is contraindicated in patients with liver failure, autoimmune conditions, or who are receiving warfarin. Long-term adverse effects of rofecoxib include hypertension, edema, and congestive heart failure, and it is contraindicated in patients with renal insufficiency or who are receiving warfarin. Melatonin is considered safe in older patients, but more caution should be taken with rofecoxib. Owing to limited evidence in support of most of the interventions we studied, none of these interventions can be recommended for routine use after TJA. Melatonin and rofecoxib may provide a benefit to sleep quality in some patients, but physicians need to understand the adverse effects and contraindications before recommending these interventions. Additionally, rofecoxib is no longer commercially available. Future investigation is warranted to evaluate the effectiveness of interventions with minimal side effect profiles for providers to be able to make an informed decision about interventions for sleep improvement after TJA. Level III, therapeutic study.