This multicenter, randomized, non-inferiority phase III trial (NCT03792100) aimed to evaluate the efficacy and safety of SmofKabiven®, a three-chamber parenteral nutrition (PN) emulsion in adult patients undergoing gastrointestinal surgery. Eligible participants were randomized to either SmofKabiven® group (SEG) (n = 135) or hospital-compounded PN group (HCG) (n = 134) for five consecutive postoperative days. The primary endpoint was the change in serum prealbumin levels from baseline to day 6, with a non-inferiority margin of -2.75 mg/dL. By day 6, change of serum prealbumin levels from baseline was 3.22 mg/dl in the SEG and 2.74 mg/dl in the HCG, with a difference of 0.48 mg/dl (95% confidence interval: -0.80 to 1.77), indicating comparable improvement in nutritional status. Linoleic acid decreased more with SEG than that with HCG (between-group difference: -7.84 mg/l, P = 0.0128), while arachidonic acid decreased more with HCG (between-group difference: 0.38 mg/l, P = 0.0025). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were significantly higher with SEG (between-group difference: EPA, 0.48 mg/l, P < 0.0001; DHA, 0.64 mg/l, P < 0.0001, respectively), and taurine levels also increased significantly (between-group difference: 14.77 µM, P = 0.0217). Treatment-related adverse events were comparable in the two groups. SmofKabiven® was comparable to hospital-compounded PN in improving postoperative nutritional status and safety profile and its enrichment with omega-3 fatty acids and taurine may provide additional benefits.