Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver, or bone. The immobilization or delivery of growth factors has been explored to improve vascularization capacity of tissue-engineered constructs; however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications including immunological responses and cancer. Here, a new method of preparing water-insoluble silk protein scaffolds with vascularization capacity using an all-aqueous process is reported. Acid is added temporally to tune the self-assembly of silk in the lyophilization process, resulting in water-insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have an appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk-based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.