Road safety is a worldwide issue, while urban roads account for a high share of serious road injuries, especially involving vulnerable road users, such as pedestrians or cyclists. Specifically, the safety of major roads through built-up areas (through-roads) is insufficient due to mixed traffic conditions including vulnerable road users, varying driving behaviour, and many disruptions, which are combined with excessive speed.. In this context, various traffic calming measures have been implemented to improve road safety, such as gateways or pedestrian refuge islands. However, the specific safety impacts of traffic calming combined with specific characteristics of through-roads are often unknown, since most traditional evaluations have been limited by small sample sizes of crash data, as well as wide variations in physical and road characteristics. To overcome the limitations of crash-based evaluations, we used the GPS-based data from a sample of 21 Czech and 12 Polish through-roads to develop the Speed-Safety Index, which combines speed, speed variance, and traffic volume. Our study has three novelty features: (1) To assess safety, we used speed and speed variance simultaneously. (2) To complete the missing link between specific traffic calming measures and safety, we validated the statistical relationship between the developed Speed-Safety Index and crash history. (3) To prove the usefulness of the developed index, we also showed its practical interpretation by proving the effect of spacing between traffic calming measures on safety. The index proved to be well correlated to crash frequency and it also proved the effect of spacing between traffic calming measures: the longer spacing, the smaller speed-reducing effect. The paper concludes with a discussion on the limitations, which we plan to address in further research, by moving from the current macro-perspective (Speed-Safety Index on the level of through-roads) to the micro-perspective (focusing on individual directions, locations, and traffic calming measures). We also plan to investigate the method’s applicability in different contexts. If the approach proves feasible, with reliable and valid results, it may become an alternative for a proactive network-wide road assessment, as called for by the European Road Infrastructure Safety Management Directive.