Recently, due to an increase in production demand in nuclear and oil and gas industries, the requirement to migrate toward larger pipe sizes for future developments has become essential. However, it is interesting to note that almost all the research on two-phase gas-liquid flow in vertical pipe upflow is based on small-diameter pipes (D < 100 mm), and the experimental work on the two-phase gas-liquid flow in large-diameter (D > 100 mm) vertical pipes is scarce. Under the above circumstances, the application of modeling tools/correlations based on small-diameter pipes in predicting flow behavior (flow pattern, void fraction, and pressure gradient) poses severe challenges in terms of accuracy. The results presented in this article are motivated by the need to introduce the research work done to the industries where the data pertaining to large-diameter vertical pipes are scarce and there is a lack of understanding of two-phase gas-liquid flow behavior in large-diameter (D > 100 mm) vertical pipes. The unique aspect of the results presented here is that the experimental data have been generated for a 254-mm inner diameter vertical pipe that forms an excellent basis for the assessment of modeling tools/correlations. This article (i) presents the results of a systematic investigation of the flow patterns in large-diameter vertical pipes and identifies the transition between subsequent flow patterns, (ii) compares it directly with the existing large- (150 mm) and small-diameter data (28 mm and 32 mm) in the same air-water superficial velocity range, (iii) exemplifies that the existing available empirical correlations/models/codes are significantly in error when applied to large- diameter vertical pipes for predictions, and last (iv) assesses the predictive capability of a well-known commercial multiphase flow simulator.