Introduction: Ventilator-associated pneumonia, a common cause of mortality and morbidity, is commonly seen among patients with endotracheal intubation due to unsafe suctioning practices by health professionals. Objective: A systematic review was conducted to explore the gaps in the existing practices of nurses and thus proposing comprehensive guidelines for safe practice. Materials and methods: A two-phase strategy was adopted to identify the studies through a comprehensive electronic search in PubMed, Google Scholar, ProQuest, Ovid, and Helinet Summon by using predefined keywords within a year limit of 2002–2016. The quality of studies was reviewed using tools endorsed by Joanna Briggs Institute. This review was conducted according to the guidelines described in the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Qualitative data were described through the process of metasynthesis. Quantitative analysis was performed to combine the competent quantitative evidences to identify knowledge and practices of endotracheal suctioning (ETS). Results: Thirty studies had been subjected for metasynthesis, among which six provided relevant information for quantitative analysis. Quantitative analysis of the studies reported that only 36% of the nurses had assessed patients prior to suctioning and had knowledge about the size of the suction catheter while only 46% were aware of the appropriate suction pressure to be used for ETS. Handwashing compliance prior to suctioning was observed in only 62% of the nurses. It is reported that, despite the awareness on possible complications, nurses fail to adhere to the recommended practice guidelines. Conclusion: The current review would explore the best evidence-based practices (EBPs) among nurses related to ETS, which would ensure quality care to critically ill patients.