To assess the comparative safety and efficacy of a new parenteral lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid20%) for postoperative patients, a meta-analysis of randomized controlled trials (RCTs) was conducted. Six RCTs with a total of 306 patients were included in the analysis. The overall quality of evidence for each outcome was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) software. Compared with a soybean-based (Lipoven20%) and a soybean- and olive oil-based (ClinOleic20%) lipid emulsion, SMOFlipid20% was associated with lower levels of hepatic enzymes, suggesting less toxicity. Changes in low-density lipoprotein triglyceride and C-reactive protein levels were also lower with SMOFlipid20% compared with Lipoven20%. Differences between SMOFlipid20% and a lipid emulsion containing medium- and long-chain triglycerides (MCT/LCT20%) were not statistically significant. For all trials, there were no significant differences in adverse events and length of hospital stay. The quality of evidence from the RCTs evaluating SMOF20% versus Lipoven20% was moderate, while most of the evidence from RCTs of SMOF20% versus ClinOleic20% and MCT/LCT20% lipid emulsions was low.