Background Timely decisions concerning mobilization and allocation of resources and distribution of casualties are crucial in medical management of major incidents. The aim of this study was to evaluate documented initial regional medical responses to major incidents by applying a set of 11 measurable performance indicators for regional medical command and control and test the feasibility of the indicators. Methods Retrospective data were collected from documentation from regional medical command and control at major incidents that occurred in two Swedish County Councils. Each incident was assigned to one of nine different categories and 11 measurable performance indicators for initial regional medical command and control were systematically applied. Two-way analysis of variance with one observation per cell was used for statistical analysis and the post hoc Tukey test was used for pairwise comparisons. Results The set of indicators for regional medical command and control could be applied in 102 of the130 major incidents (78%), but 36 incidents had to be excluded due to incomplete documentation. The indicators were not applicable as a set for 28 incidents (21.5%) due to different characteristics and time frames. Based on the indicators studied in 66 major incidents, the results demonstrate that the regional medical management performed according to the standard in the early phases (1–10 min after alert), but there were weaknesses in the secondary phase (10–30 min after alert). The significantly lowest scores were found for Indicator 8 (formulate general guidelines for response) and Indicator 10 (decide whether or not resources in own organization are adequate). Conclusions Measurable performance indicators for regional medical command and control can be applied to incidents that directly or indirectly involve casualties provided there is sufficient documentation available. Measurable performance indicators can enhance follow- up and be used as a structured quality control tool as well as constitute measurable parts of a nationally based follow-up system for major incidents. Additional indicators need to be developed for hospital-related incidents such as interference with hospital infrastructure.