Supercritical impregnation can be used for the elaboration of controlled release systems that may be applied to pharmaceutical and medicinal fields. The present work is dedicated to the impregnation of intraocular lenses (IOLs) with antibiotics using supercritical carbon dioxide as impregnation vector. Commercially available intraocular lenses have been impregnated with cefuroxime sodium in order to obtain ophthalmic drug delivery systems dedicated to the prevention of postoperative endophthalmitis in cataract surgery. The influence of the variation of some experimental operating conditions such as the pressure (8–20 MPa), the temperature (308 and 333 K), the impregnation duration (1–5 h), the addition of a cosolvent (ethanol) or the depressurisation rate (slow and rapid depressurisation) has been studied. In certain experimental conditions, foaming phenomena have been observed. In order to evaluate the impregnation efficiency, the impregnation yields were quantified gravimetrically and the drug release profiles were determined through in vitro drug release studies carried out at 310 K and in a solution simulating the aqueous humor. At rapid depressurisation rates, controlled drug release IOLs with impregnation yields varying between 0.002 and 0.063 mgdrug/mgIOL were obtained. Increasing the pressure or adding a cosolvent were favourable to enhance the impregnation yields. However, a non desired foaming phenomenon was observed for the most favourable conditions. By carrying out slow depressurisations, foaming phenomena were avoided. Nevertheless, in these conditions, the impregnation process was less efficient. The drug partition seems to be more favourable towards the supercritical phase than towards the polymer and the impregnation phenomena governed by a deposition mechanism rather than a molecular dispersion of the active ingredient. The drug is almost deposited within the porosity created during the rapid depressurisation phase. This result was confirmed by the results of the drug release studies.