Microfluidics has experienced a significant increase in research activities in recent years with a wide range of applications emerging, such as micro heat exchangers, energy conversion devices, microreactors, lab-on-chip devices and micro total chemical analysis systems (μTAS). Efforts to enhance or extend the performance of single phase microfluidic devices are met by two-phase flow systems [1, 2]. Essential for the design and control of microfluidic systems is the understanding of the fluid/hydrodynamic behavior, especially pressure drop correlations. These are well established for single phase flow, however, analytical correlations for two-phase flow only reflect experimentally obtained values within an accuracy of ± 50% [3, 4]. The present study illustrates the effect of two-phase flow regimes on the pressure drop. Experimental measurement data is put into relation of calculated values based on established correlations of Lockhart-Martinelli with Chisholm modifications for macroscopic flows [5, 6] and Mishima-Hibiki modifications for microscale flows [7]. Further, the experimental pressure drop data is superimposed onto two-phase flow maps to identify apparent correlations of pressure drop abnormalities and flow regimes. The experiments were conducted in a square microchannel with a width of 200 μm. Optical access is guaranteed by an anodically bonded glass plate on a MEMS fabricated silicon chip. Superficial velocities range from 0.01 m/s to 1 m/s for the gas flow and from 0.0001 m/s to 1 m/s for the liquid flow with water as liquid feed and CO2 as gas. The analysis of the flow regimes was performed by imaging the distinct flow regimes by laser induced fluorescence microscopy, employing Rhodamine B as the photosensitive dye. The pressure drop was synchronically recorded with a 200 mbar, 2.5 bar and 25 bar differential pressure transmitter and the data was exported via a LabView based software environment, see Figure 1. Figure 2 illustrates the experimentally obtained pressure drop in comparison to the calculated values based on the Lockhard-Martinelli correlation with the Chisholm modification and the Mishima-Hibiki modification. For both cases the predications underestimate the two-phase pressure drop by more than 50%. Nevertheless, the regression of the experimental data has an offset of linear nature. Two-phase flow is assigned to flow regime maps of bubbly, wedging, slug or annular flow defined by superficial gas and liquid velocities. In Figure 3 the pressure drop is plotted as a surface over the corresponding flow regime map. Transition lines indicate a change of flow regimes enclosing an area of an anticline in the pressure data. In the direct comparison between the calculated and the measured values, the two surfaces show a distinct deviation. Especially, the anticline of the experimental data is not explained by the analytical correlations. Figure 4 depicts the findings of Figure 3 at a constant superficial velocity of 0.0232 m/s. The dominant influence of the flow regimes on the pressure drop becomes apparent, especially in the wedging flow regime. The evident deviation of two-phase flow correlations for the pressure drop is based on omitting the influence of the flow regimes. In conclusion, the study reveals a strong divergence of pressure drop measurements in microscale two-phase flow from established correlations of Lockhart-Martinelli and recognized modifications. In reference to [8, 9], an analytical model incorporating the flow regimes and, hence, predicting the precise pressure drop would be of great benefit for hydrodynamic considerations in microfluidics.