Microvascular networks undergo patterning changes that determine and reflect functional adaptations during tissue remodeling. Alterations in network architectures are a result of complex and integrated signaling events. To understand how two growth factor signals interact to stimulate angiogenesis and arterialization, we engineered spatially-directed microvascular pattern changes in vivo using combinations of focally-delivered exogenous growth factors. We implanted microdelivery beads containing recombinant vascular endothelial growth factor₁₆₄ (VEGF₁₆₄) and angiopoietin-1* (Ang-1*) into the dorsal subcutaneous tissue of fully anesthetized male Fischer 344 rats implanted with backpack window chambers and quantified vascular patterning changes using intravital microscopy, a combination of architectural metrics, and immunohistochemistry. Focal delivery of VEGF₁₆₄ caused spatially directed increases in both the total number and the density of vessels with diameters less than 25 µm 7 days after microbead implantation. Increases were maintained out to 14 days, but were reduced to control values by day 21. Adding Ang-1* on day 7 maintained these increases out to day 21, induced vessel order ratios comparable to control levels, and was accompanied by increases in the length density of smooth muscle -actin (SMA) positive vessels. We achieved spatial control of patterning changes in vivo using multisignal stimulation via focal delivery of exogenous growth factor combinations, and conclude that Ang-1* administered subsequent to VEGF₁₆₄ stimulation induces vascular growth while maintaining a network pattern consistent with native patterns that persist in the presence of vehicle control stimulation.