Abstract Objective To derive and validate a mathematical model to predict laser-induced temperature changes in a kidney during kidney stone treatment. Methods A simplified mathematical model to predict temperature change in the kidney for any given renal volume, irrigation flow rate, irrigation fluid temperature, and laser power was derived. We validated our model with matched in vitro experiments. Results Excellent agreement between the mathematical model predictions and laboratory data was obtained. Conclusion The model obviates the need for repeated experimental validation. The model predicts scenarios where risk of renal tissue damage is high. With real-time knowledge of flow rate, irrigating fluid temperature and laser usage, safety warning levels could be predicted. Meanwhile, clinicians should be aware of the potential risk from thermal injury and take measures to reduce the risk, such as using room temperature irrigation fluid and judicious laser use.