Abstract Aims Identification of patients at high-risk of surgical-site infections (SSI) may allow surgeons to minimise associated morbidity. However, there are significant concerns with the methodological quality and transportability of models previously developed. We aimed to develop a novel score to predict 30-day SSI risk following gastrointestinal surgery across a global context, and externally validate against existing models. Methods This was a secondary analysis of 2 prospective international cohort studies: GlobalSurg-1 (July-November 2014) and GlobalSurg-2 (January-July 2016). Consecutive adults undergoing gastrointestinal surgery were eligible. Model development was performed in GlobalSurg-2 data, with novel and previous scores externally validated in GlobalSurg-1. The primary outcome was 30-day SSI, with two predictive techniques explored: penalised regression (LASSO) and machine learning (XGBOOST). Final model selection based on prognostic accuracy and clinical utility. Results There were 14,019 patients (SSI=12.3%) for derivation, and 8,464 (SSI=11.4%) for external validation. The LASSO model was selected due to similar discrimination to XGBoost (AUC: 0.738, 0.725-0.750 versus 0.737, 0.709-0.765), but greater explainability. The final score included six variables: country income, ASA grade, diabetes, and operative contamination, approach, and duration. Model performance remained good on external validation (AUC: 0.730, 0.715-0.744; calibration-in-the-large: -0.098, slope: 1.008), and demonstrated superior performance to external validation of all previous models. Conclusion The GloSSI score allowed accurate prediction of the risk of SSI with 6 simple variables which are routinely available at the time of surgery across global settings. This can inform use of intraoperative and postoperative interventions to modify the risk of SSI and minimise associated harm.