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Dry eye is a common eye condition with significant impact on its sufferers’ quality of life. We conducted a systematic review of randomized controlled treatment trials to assess the effectiveness of lipid-containing lubricants (LCLs) on dry eye treatment.An online database was searched without any language or date restrictions. Clinical trials on LCL with non-lipid-containing control eyedrops were included. The outcome measures of each study (including symptoms and clinical signs), their risk of bias (assessed using the Cochrane tool), and strength of evidence were discussed.Three studies on liposomal lid sprays and four on lipid-containing eyedrops were included. All studies found significant improvements in most of the symptoms/signs of dry eye in patients who used LCL during the study period. Subjects in all trials reported greater symptom relief with LCLs, although this was shown to be short lived in two studies. Lipid layer structure improvement after LCLs application was demonstrated in two studies, although only up to 90 min in one study. Improvement in Schirmer test results was shown in two out of four studies, tear breakup time in four out of five studies, meibomian gland status in three out of three studies, conjunctival folds and tear evaporation rates in two out of two studies each. None of the studies were completely free of risks of bias; only three studies were double masked. Three of the studies were assigned high level of evidence, three were assigned as moderate evidence, and the final one low level of evidence.Most studies have demonstrated the effectiveness of LCLs on improving select signs of dry eye. Based on the overall substantial level of evidence, this type of eyedrop can be recommended for use in clinical practice where the aim is to reduce the signs and symptoms of dry eye.