With oil and gas exploitation developing towards deep-water fields, the extreme, low-temperature, and high-pressure environments are ideal for hydrate formation in subsea pipelines. Hydrate formation, growth, aggregation, and deposition in the flowlines substantially increase the hydrate blockage risk, necessitating the assessment and clarification of this process. This work employed computational fluid dynamics (CFD) and the discrete element method (DEM) to perform several numerical simulations using Fluent and EDEM to study the hydrate blockage process caused by aggregation and deposition. A three-dimensional model of a solid-liquid pipeline containing hydrate particles was established, which considered the cohesion force between the hydrate particles and the adhesion force between the hydrate particles and pipe wall. Two simulation strategies were implemented. The first simulated the hydrate blockage process using a throttling element, which assumed hydrate depositions on the pipeline wall. The second studied the impact of the collision between upstream and downstream hydrate aggregates. The critical hydrate blockage state was roughly defined based on the hydrate volume fraction and pressure drop changes during the hydrate aggregate collision process. These results represented the initial work for simulating the hydrate blockage process via combined CFD-DEM by considering the bidirectional interaction between the continuous water phase and discrete hydrate particles. These preliminary findings provided theoretical support for studying the hydrate blockage mechanism to solve the hydrate flow assurance issue in the subsea pipelines.