Aims. Though most humeral shaft fractures heal nonoperatively, up to one-third may lead to nonunion with inferior outcomes. The Radiographic Union Score for HUmeral Fractures (RUSHU) was created to identify high-risk patients for nonunion. Our study evaluated the RUSHU’s prognostic performance at six and 12 weeks in discriminating nonunion within a significantly larger cohort than before. Methods. Our study included 226 nonoperatively treated humeral shaft fractures. We evaluated the interobserver reliability and intraobserver reproducibility of RUSHU scoring using intraclass correlation coefficients (ICCs). Additionally, we determined the optimal cut-off thresholds for predicting nonunion using the receiver operating characteristic (ROC) method. Results. The RUSHU demonstrated good interobserver reliability with an ICC of 0.78 (95% CI 0.72 to 0.83) at six weeks and 0.77 (95% CI 0.71 to 0.82) at 12 weeks. Intraobserver reproducibility was good or excellent for all analyses. Area under the curve in the ROC analysis was 0.83 (95% CI 0.77 to 0.88) at six weeks and 0.89 (95% CI 0.84 to 0.93) at 12 weeks, indicating excellent discrimination. The optimal cut-off values for predicting nonunion were ≤ eight points at six weeks and ≤ nine points at 12 weeks, providing the best specificity-sensitivity trade-off. Conclusion. The RUSHU proves to be a reliable and reproducible radiological scoring system that aids in identifying patients at risk of nonunion at both six and 12 weeks post-injury during non-surgical treatment of humeral shaft fractures. The statistically optimal cut-off values for predicting nonunion are ≤ eight at six weeks and ≤ nine points at 12 weeks post-injury