This paper focuses on a new comprehensive probabilistic approach for lifetime risk assessment of buildings equipped with active vibration control systems under future probable mainshock-aftershock scenarios. This procedure starts from the seismic hazard simulation, continues with the building performance evaluation, and ends with the seismic risk assessment. The procedure attempts to reflect the effects of major uncertainty sources existing in both building properties and earthquake scenarios using the Monte-Carlo simulation technique. The method is applied to steel moment-resisting frame buildings armed with the optimally designed active vibration control system (using the linear quadratic regulator algorithm). In each realization of the Monte-Carlo simulation, first, a random earthquake scenario containing probable future mainshock-aftershock sequences and their corresponding synthetic stochastic accelerograms are procreated. Next, the buildings are designed in two separate cases, with and without the presence of active vibration control systems. The former is designed based on the international design codes, while the latter properties are obtained via an advanced optimization method. In the last step, considering all generated samples, the loss curve of buildings with the active control system is developed for two separate cases: with or without taking aftershocks’ effects into account. The application of this method indicates that the active control system works well in decreasing the loss value (on average 66%) of buildings during their 50-year lifetime, especially in the more intensive earthquake scenarios. Additionally, it is shown that by neglecting the aftershocks, the life-cycle cost of building will be estimated tangibly (on average 70%) less than what it would be. Finally, it is observed that the non-structural acceleration-sensitive damages have a higher contribution in total building losses in uncontrolled structures in comparison with the actively controlled building by considering aftershocks.