The strength and stability of hybrid fiber delivery systems, ones that perform a mechanical function and simultaneously deliver drug, are critical in the design of surgically implantable constructs. We report the fabrication of drug-eluting microfibers where drug loading and processing conditions alone increase microfiber strength and stability partially due to solvent-induced crystallization. Poly(l-lactic acid) microfibers of 64±7μm diameter were wet spun by phase inversion. Encapsulation of a model hydrophobic anti-inflammatory drug, dexamethasone, at high loading provided stability to microfibers which maintained linear cumulative release kinetics up to 8weeks in vitro. In our wet spinning process, all microfibers had increased crystallinity (13–17%) in comparison to unprocessed polymer without any mechanical stretching. Moreover, microfibers with the highest drug loading retained 97% of initial tensile strength and were statistically stronger than all other microfiber formulations, including control fibers without drug. Results indicate that the encapsulation of small hydrophobic molecules (<400Da) may increase the mechanical integrity of microfilaments whose crystallinity is also increased as a result of the process. Multifunctional drug-eluting microfibers can provide an exciting new opportunity to design novel biomaterials with mechanical stability and controlled release of a variety of therapeutics with micron-scale accuracy.