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Background To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. Methods and findings In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I.sup.2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I.sup.2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I.sup.2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I.sup.2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I.sup.2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I.sup.2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). Conclusions Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity., Author(s): Gifty Marley 1,2, Xia Zou 3, Juan Nie 4, Weibin Cheng 5,6, Yewei Xie 2, Huipeng Liao 2, Yehua Wang 2, Yusha Tao 2, Joseph D. Tucker 2,7, Sean [...]