Despite the attractive features of nanofibrous scaffolds for cell attachment in tissue-engineering (TE) applications, impeded cell ingrowth has been reported in electrospun scaffolds. Previous findings have shown that the scaffold can function as a sieve, keeping cells on the scaffold surface, and that cell migration into the scaffold does not occur in time. Because fiber diameter is directly related to the pore size of an electrospun scaffold, the objective of this study was to systematically evaluate how cell delivery can be optimized by tailoring the fiber diameter of electrospun poly(ε- caprolactone) (PCL) scaffolds. Five groups of electrospun PCL scaffolds with increasing average fiber diameters (3.4-12.1μm) were seeded with human venous myofibroblasts. Cell distribution was analyzed after 3 days of culture. Cell penetration increased proportionally with increasing fiber diameter. Unobstructed delivery of cells was observed exclusively in the scaffold with the largest fiber diameter (12.1 μm). This scaffold was subsequently evaluated in a 4-week TE experiment and compared with a poly(glycolic acid)-poly(4- hydroxybutyrate) scaffold, a standard scaffold used successfully in cardiovascular tissue engineering applications. The PCL constructs showed homogeneous tissue formation and sufficient matrix deposition. In conclusion, fiber diameter is a crucial parameter to allow for homogeneous cell delivery in electrospun scaffolds. The optimal electrospun scaffold geometry, however, is not generic and should be adjusted to cell size. © 2009, Mary Ann Liebert, Inc.