Infectious bovine rhinotracheitis (IBR) is a critical respiratory disease affecting calves worldwide; however, the optimal schedule for inactivated IBR vaccination remains unknown. This study investigated the reactivity induced by inactivated IBR vaccine and its related factors in Holstein calves following a modified live vaccine schedule. IBR reactivity in 94 calves was investigated. Calves were classified based on changes in IBR reactivity from pre-vaccination to 8 weeks post-vaccination. Factors associated with changes in IBR reactivity were evaluated. IBR reactivity levels decreased in 62.8% calves despite vaccination, whereas those of calves with low pre-vaccination IBR reactivity levels increased. Analysis of IBR reactivity according to birth weight revealed that calves born overweight had high IBR reactivity levels pre-vaccination, and vaccination failed to increase reactivity levels in 88.2% of these calves. Improvement in IBR reactivity was not necessarily associated with pre-vaccination IBR reactivity levels. The >20% decrease classifications showed lower IBR reactivity at pre-vaccination than the <20% decrease classifications. The classifications that showed better improvement in IBR reactivity had higher monocyte, monocyte-to-lymphocyte ratio, lactate dehydrogenase, and creatine kinase values at pre-vaccination. These results indicate that the schedule for inactivated IBR vaccination is ineffective in calves, birth weight may be related to passive immunity in IBR reactivity, and inactivated IBR vaccine-induced reactivity may be associated with the identified four blood parameters and passive immunity. Subsequent investigations are necessary to establish an appropriate timetable for inactivated IBR vaccination and uncover mechanisms underlying the relationship between the four blood parameters and inactivated IBR vaccination.