The effect of selected formulation variables on the release of chlorhexidine from poly(ε-caprolactone) films was evaluated in vitro using a complete factorial experimental design. Repeated measures analysis of variance showed chlorhexidine type (diacetate or base), drug load (10, 20 or 30% w/w), chlorhexidine particle size (< 63 or 63−125 μm) and film side (upper or lower) significantly affected the percentage released over 10 and 30 days. Significant interactions were also observed between factors. Release from the upper side of films occurred more slowly than from the lower side of films for most formulations. This difference was particularly apparent for films containing chlorhexidine diacetate. The general release equation ( M t / M ∞ = kt n ) was fitted to the release data and constants estimated. The value of n, which indicates the mechanism of release, tended towards 0.5 for release at high drug loadings which may suggest release was predominantly diffusion-controlled from these films. Transecting sections of film, prepared with chlorhexidine diacetate < 63 μm (drug loading 20% w/w), and analysing the chlorhexidine content at varying distances from the film surfaces showed a gradient in chlorhexidine concentration through the film, with lower concentrations near the upper side and higher concentrations near the lower side.