Bioactive, patterned micro- and nanoscale surfaces that can be spatially engineered for three-dimensional ligand presentation and sustained release of signaling molecules represent a critical advance for the development of next-generation diagnostic and therapeutic devices. Lithography is ideally suited to patterning such surfaces due to its precise, easily scalable, high-throughput nature; however, to date polymers patterned by these techniques have not demonstrated the capacity for sustained release of bioactive agents. Here a class of lithographically defined, electropolymerized polymers with monodisperse micro- and nanopatterned features capable of sustained release of bioactive drugs and proteins is demonstrated. It is shown that precise control can be achieved over the loading capacity and release rates of encapsulated agents and this aspect is illustrated using a fabricated surface releasing a model antigen (ovalbumin) and a cytokine (interleukin-2) for induction of a specific immune response. Furthermore, the ability of this technique to enable three-dimensional control over cellular encapsulation is demonstrated. The efficacy of the described approach is buttressed by its simplicity, versatility, and reproducibility, rendering it ideally suited for biomaterials engineering.