We introduce the use of silicon (Si) as a substrate for the electroformation of giant phospholipid vesicles. By taking advantage of the tunability of silicon surface properties, we varied the organization of the phospholipid film on the electrode and studied the consequences on vesicle formation. In particular, we investigated the effects of Si surface chemistry and microtopology on the organization of the phospholipid film and the properties of the final vesicles. We established correlations between chemical homogeneity, film defects, and resulting vesicle size distribution. By considering phospholipid films that are artificially fragmented by electrode microstructures, we showed that the characteristic size of vesicles decreases with a decrease in microstructure dimensions. We finally proposed a way to control the vesicle size distribution by using a micropatterned silicon dioxide layer on a Si substrate.