Background: Most patients with Crohn's disease (CD), a chronic inflammatory disease, need surgery but exhibit elevated postoperative complication incidences. ω-3 polyunsaturated fatty acids (PUFAs) are considered beneficial for nutrition, anti-inflammation, immunity and intestinal microflora balance in humans. This study assessed the effects of ω-3 PUFA-supplemented parenteral nutrition (PN) on postoperative complications in CD.Methods: Overall, 186 CD patients undergoing bowel resection were eligible. Patient data were collected from a prospectively maintained database. After surgery, 103 patients received ω-3 PUFA-supplemented PN; 83 did not. Postoperative complications were compared between the groups. Complication risk factors were identified by univariate and multivariate analyses.Results: Patients with ω-3 PUFA-supplemented PN after surgery had lower C-reactive protein levels (57.2±5.3 mg/L vs 43.5±3.9 mg/L, P=0.047) and shorter postoperative hospital stays (12.1±1.1 days vs 9.3±0.6 days, P=0.041) than those without. The ω-3 PUFA group exhibited significantly reduced incidences of overall complications (40.8% vs 24.1%, P=0.016) and major complications (23.3% vs 9.6%, P=0.014). Postoperative complications were associated with infliximab, ω-3 PUFAs, C-reactive protein, operative time, and laparoscopic surgery. Multivariate regression revealed that preoperative infliximab use and postoperative ω-3 PUFA-supplemented PN were independent risk factors in CD. Conclusions: ω-3 PUFA-supplemented PN reduced post-surgery inflammatory response in CD patients, thus decreasing postoperative complications and accelerating recovery.Trial registration: This trial was registered in ClinicalTrials.gov. Identifier was NCT03901937. The date of registration was 03/04/2019.