Integrated circuit susceptibility to radiation-induced faults remains a major reliability concern. The continuous downscaling of device feature size and the reduction in supply voltage in CMOS technology tend to worsen the problem. Thus, the evaluation of Soft Error Rate (SER) in the presence of multiple transient faults is necessary, since it remains an open research field. In this work, a Monte-Carlo simulation-based methodology is presented taking into consideration the masking mechanisms and placement information. The proposed SER estimation tool exploits the results of a Single Event Transient (SET) pulse characterization process with HSPICE to obtain an accurate assessment of circuit vulnerability to radiation. A new metric, called Glitch Latching Probability, which represents the impact of the masking effects on a SET, is introduced to identify gate sensitivity and, finally, experimental results on a set of ISCAS’ 89 benchmarks are presented.