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Background: Preterm birth is the leading cause of under-five-mortality worldwide, with the highest burden in low-income and middle-income countries (LMICs). The aim of this study was to synthesise evidence-based interventions for preterm and low birthweight (LBW) neonates in LMICs, their associated neonatal mortality rate (NMR), and barriers and facilitators to their implementation. This study updates all existing evidence on this topic and reviews evidence on interventions that have not been previously considered in current WHO recommendations., Methods: Six electronic databases were searched until 3 March 2020 for randomised controlled trials reporting NMR of preterm and/or LBW newborns following any intervention in LMICs. Risk ratios for mortality outcomes were pooled where appropriate using a random effects model (PROSPERO registration number: CRD42019139267)., Results: 1236 studies were identified, of which 49 were narratively synthesised and 9 contributed to the meta-analysis. The studies included 39 interventions in 21 countries with 46 993 participants. High-quality evidence suggested significant reduction of NMR following antenatal corticosteroids (Pakistan risk ratio (RR) 0.89; 95% CI 0.80 to 0.99|Guatemala 0.74; 0.68 to 0.81), single cord (0.65; 0.50 to 0.86) and skin cleansing with chlorhexidine (0.72; 0.55 to 0.95), early BCG vaccine (0.64; 0.48 to 0.86; I 2 0%), community kangaroo mother care (OR 0.73; 0.55 to 0.97; I 2 0%) and home-based newborn care (preterm 0.25; 0.14 to 0.48|LBW 0.42; 0.27 to 0.65). No effects on perinatal (essential newborn care 1.02; 0.91 to 1.14|neonatal resuscitation 0.95; 0.84 to 1.07) or 7-day NMR (essential newborn care 1.03; 0.83 to 1.27|neonatal resuscitation 0.92; 0.77 to 1.09) were observed after training birth attendants., Conclusion: The findings of this study encourage the implementation of additional, evidence-based interventions in the current (WHO) guidelines and to be selective in usage of antenatal corticosteroids, to reduce mortality among preterm and LBW neonates in LMICs. Given the global commitment to end all preventable neonatal deaths by 2030, continuous evaluation and improvement of the current guidelines should be a priority on the agenda., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)