Minimizing misalignments during the interconnection of microfluidic modules is extremely critical to develop a fully integrated microfluidic device. Misalignments arising during chip-to-chip or world-to-chip interconnections can be greatly detrimental to efficient functioning of microfluidic devices. To address this problem, we have performed numerical simulations to investigate the effect of misalignments arising in three types of interconnection methods: (i) end-to-end interconnection (ii) channel overlap when chips are stacked on top of each other, and (iii) tube-in-reservoir misalignment occurring due to the offset between the external tubing and the reservoir. For the case of end-to-end interconnection, the effect of misalignment was investigated for 0, 13, 50, 58, and 75% reduction in the available flow area at the location of geometrical misalignment. In the channel overlap interconnection method, various possible misalignment configurations were simulated by maintaining the same amount of misalignment (75% flow area reduction). The effect of misalignment in a tube-in-reservoir interconnection was investigated by positioning the tube at an offset of 164m from the reservoir center. All the results were evaluated in terms of the equivalent length of a straight pipe. The effect of Reynolds number (Re) was also taken into account by performing additional simulations of aforementioned cases at Re ranging between 0.075 Re 75. Correlations were developed and the results were interpreted in terms of equivalent length (L-e). Equivalent length calculations revealed that the effect of misalignment in tube-in-reservoir interconnection method was the least significant when compared to the other two methods of interconnection.