Currently, reservoir fluid compositions (based on PVT reports) are used in predicting the hydrate stability zone. However, in multiphase flow there are variations in the local composition that may affect the hydrate stability zone. The main objective of this work was to investigate the effect of hold-up and the resulting variation in the local composition on the hydrate stability zone of various hydrocarbon systems. A thermodynamic software was used to predict the composition of various phases at different locations along a pipeline. A range of liquid hold-ups were assumed and the local composition was recalculated. The hydrate option of the software was used to predict the hydrate stability zone of the resulting local fluid composition. The calculations were repeated for a number of fluid systems and the results are presented in this work. The calculated hydrate stability zones for various hold-ups were compared with that of original reservoir fluid. The results show that hold-up plays an important role on the hydrate stability zone. High gas hold-up shifts the hydrate stability zone to the right. However, as high gas hold-ups occurs at high point and away from aqueous phase, in case of changes in the system conditions the amount of hydrates are limited to the amount of water available. This paper demonstrates that the hydrate stability zone of a multiphase fluid in a pipeline is a function of hold-up and the resulting changes in the local composition. This could have important consequences on the hydrate prevention strategies.