Background: Identifying and managing serious spinal pathology (SSP) such as cauda equina syndrome or spinal infection in patients presenting with low back pain is challenging. Traditional red flag questioning is increasingly criticized, and previous studies show that many clinicians lack confidence in managing patients presenting with red flags. Improving decision-making and reducing the variability of care for these patients is a key priority for clinicians and researchers. Objective: We aimed to improve SSP identification by constructing and validating a decision support tool using a Bayesian network (BN), which is an artificial intelligence technique that combines current evidence and expert knowledge. Methods: A modified RAND appropriateness procedure was undertaken with 16 experts over 3 rounds, designed to elicit the variables, structure, and conditional probabilities necessary to build a causal BN. The BN predicts the likelihood of a patient with a particular presentation having an SSP. The second part of this study used an established framework to direct a 4-part validation that included comparison of the BN with consensus statements, practice guidelines, and recent research. Clinical cases were entered into the model and the results were compared with clinical judgment from spinal experts who were not involved in the elicitation. Receiver operating characteristic curves were plotted and area under the curve were calculated for accuracy statistics. Results: The RAND appropriateness procedure elicited a model including 38 variables in 3 domains: risk factors (10 variables), signs and symptoms (17 variables), and judgment factors (11 variables). Clear consensus was found in the risk factors and signs and symptoms for SSP conditions. The 4-part BN validation demonstrated good performance overall and identified areas for further development. Comparison with available clinical literature showed good overall agreement but suggested certain improvements required to, for example, 2 of the 11 judgment factors. Case analysis showed that cauda equina syndrome, space-occupying lesion/cancer, and inflammatory condition identification performed well across the validation domains. Fracture identification performed less well, but the reasons for the erroneous results are well understood. A review of the content by independent spinal experts backed up the issues with the fracture node, but the BN was otherwise deemed acceptable. Conclusions: The RAND appropriateness procedure and validation framework were successfully implemented to develop the BN for SSP. In comparison with other expert-elicited BN studies, this work goes a step further in validating the output before attempting implementation. Using a framework for model validation, the BN showed encouraging validity and has provided avenues for further developing the outputs that demonstrated poor accuracy. This study provides the vital first step of improving our ability to predict outcomes in low back pain by first considering the problem of SSP.