This paper aims at collating and reviewing all data collected using the ESCA (Ecological Status of Coralligenous Assemblages) index from 2009 to 2018 during different local applications, in order to evaluate at large spatial scale its effectiveness and temporal variability. To this scope, the large-scale response of ESCA to anthropogenic disturbance was tested comparing ESCA values calculated at 42 sites of the Western Mediterranean Sea with the anthropization index. Moreover, the sensitivity of ESCA to punctual human disturbance and the robustness of the index across the natural space and time variability were evaluated. The large spatial scale study showed significant correlation between ESCA and the anthropization index, while very low correlation was detected when descriptors of ESCA (i.e., sensitivity levels, α-diversity, and β-diversity) were considered separately. The three impact evaluation studies highlighted significantly lower values of the ESCA index in disturbed conditions than in the control ones. The coastal monitoring study confirmed the robustness of the index which showed a high ecological quality of coralligenous reefs in reference conditions compared to more anthropized sites, and this pattern was maintained throughout the ten years study period. Application of the ESCA index to different situations tested positively its sensibility to different levels and type of human disturbance and its stability with respect to regional spatio-temporal variability. This confirm the reliability of the ESCA index already tested on the local and annual scale, thus broadening its range of application and validating it on a wider space–time scale.