BACKGROUND Enhanced recovery after surgery is steadily gaining importance in patients undergoing pancreatic surgery, including pancreatoduodenectomy (PD). While clinical pathways targeting enhanced-recovery can achieve their intended outcome in reducing length of stay, compliance to these pathways, and their relevance is poorly understood. The aim of this systematic review was to assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes. AIM To assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes. METHODS A systematic review of major reference databases was undertaken, according to preferred reporting items for systematic reviews and meta-analysis guidelines, between January 2000 and November 2020 relating to compliance with clinical pathways and its impact on outcomes in patients undergoing PD. A meta-analysis was performed using fixed-effects or random-effects models. RESULTS Eleven studies including 1852 patients were identified. Median overall compliance to all components of the clinical pathway was 65.7% [interquartile range (IQR): 62.7%-72.3%] with median compliance to post-operative parameters of the clinical pathway being 44% (IQR: 34.5%-52.25%). Meta-analysis using a fixed-effects model showed that ≥ 50% compliance to a clinical pathway predicted significantly fewer post-operative complications [pooled odds ratio (OR): 9.46, 95% confidence interval (CI): 5.00-17.90; P < 0.00001] and a significantly shorter length of hospital stay [pooled mean difference (MD): 4.32, 95%CI: -3.88 to -4.75; P < 0.0001]. At 100% compliance which was associated with significantly fewer post-operative complications (pooled OR: 11.25, 95%CI: 4.71-26.84; P < 0.00001) and shorter hospital stay (pooled MD of 4.66, 95%CI: 2.81-6.51; P < 0.00001). CONCLUSION Compliance to post-PD clinical pathways remains low. Deviations are associated with an increased risk of complications and length of hospital stay. Under-standing the relevance of deviations to clinical pathways post-PD presents pancreatic surgeons with opportunities to actively pursue an enhanced-recovery of their patients.