Understanding groundwater dynamics at the regional scale (> 100 km) is essential to the development of sustainable water management regulations. Groundwater flow models are increasingly used to support these strategies. However, in order to be reliable, these models need to be calibrated and validated. The objective of this work is to evaluate the benefits and the limitations of using isotope-derived groundwater travel times and major ion chemistry to validate a regional-scale groundwater flow model in the humid continental climate of southern Québec (Canada). A 3D regional-scale steady-state groundwater model was created using MODFLOW for the fractured bedrock aquifer of the Centre-du-Québec region (Québec, Canada), using data acquired during recent aquifer characterization projects. The model covers an area of 7452 km 2 , from the unconfined Appalachian Mountains to the confined St. Lawrence Platform. Groundwater travel times were simulated for 211 wells using particle tracking. The groundwater flow model was calibrated using 11 775 regionally distributed heads and 15 baseflow values. The model was validated using 23 3 H/ 3 He residence time (3 to 60 years), 17 14 C residence time (226 to 22 600 years), and the major ion compositions from 211 wells. Results indicate that the model is able to satisfactorily simulate ³H/³He isotopic residence time, while 14 C isotopic residence times are generally underestimated. These results suggest substantial mixing between groundwater recharged during the last deglaciation and recently recharged water. Regional groundwater flow is limited or absent, and most of the recharge discharges to the river network as baseflow. The analysis of travel times indicates a statistically distinct mean travel time for the different groundwater types. Median travel time is 68 years for recently recharged groundwater (Ca-HCO3), 274 years for semi-confined groundwater (Na-HCO3), and 738 years for confined groundwater (Na-Cl). This confirms that groundwater chemistry is a broad indicator of groundwater travel time. Résumé La compréhension de la dynamique régionale (> 100 km) de l'eau souterraine est essentielle au développement d'une règlementation orientée vers le développement durable de cette ressource. Les modèles d'écoulement de l'eau souterraine sont de plus en plus utilisés pour supporter ces stratégies. Par contre, pour être utilisés à des fins de règlementation, ces modèles doivent être calés et validés. L'objectif de ce travail est d'évaluer les avantages et les limites de l'utilisation de l'âge isotopique de l'eau souterraine et de la géochimie des ions majeurs pour valider un modèle régional de l'écoulement de l'eau souterraine dans le climat continental humide du sud du Québec (Canada). En utilisant les données acquises dans le cadre de projets de caractérisation hydrogéologiques récents, un modèle 3D régional en régime permanent a été construit avec MODLOW afin de représenter l'aquifère fracturé de la région du Centre-du-Québec (Québec, Canada). Le modèle couvre une superficie de 7...