The aim of the study was to assess the stability of all-in-one (AIO) parenteral admixture used for neonates, containing SMOFlipid, an alternative to soybean, an α-tocopherol-enriched lipid emulsion. SMOFlipid, consisting of soybean oil, medium chain triglycerides, olive oil and fish oil, was introduced commercially in 2005. Stability assays consisted of the assessment of the admixture's macroscopic aspect, droplet size distribution, pH, peroxide value and α-tocopherol concentration. The admixture was stored at room temperature or at 4°C and analysed over time (0, 24 and 48 h). The SMOFlipid-containing AIO parenteral admixture was shown to be physicochemically stable. All changes were reversible, the droplet size was under the upper limit (0.5 µm) set by the US Pharmacopeia, maximum loss for vitamin E was 25% and the lipid peroxidation occurred within 24 h after preparation. In conclusion, the addition of SMOFlipid to an AIO parenteral admixture for neonates did not affect its physicochemical stability, and it was safe for administration on the first day of its preparation.