We have fabricated surface-modified paclitaxel nanowires (SM-PNs) with a precise diameter and an average length of 50 μm. The surface of these nanowires is coated with a monolayer of octadecylsiloxane (ODS), which prevents aggregation and enhances dispersivity in aqueous media. This system constitutes a novel drug delivery vehicle based on one-dimensional (1D) nanostructures with a large drug to vehicle ratio. We assayed the cytotoxicity of different diameter SM-PNs (200, 80, 35, and 18 nm) with U937 cells and compared their activity to microcrystalline paclitaxel. SM-PNs reduced U937 cell proliferation in culture followed by cell death. For the same amount of paclitaxel, different diameter SM-PNs displayed different cytotoxic effect at the same incubation time period. SM-PNs with 35 nm diameters were the most efficient in completely halting cell proliferation following the first 24 hours of treatment, associated with 42% cell death. SM-PNs with 18 nm diameters were least effective. These SM-PNs can be tailored to fit a certain treatment protocol by simply choosing the appropriate diameter.