Polymer fabrics are used in different areas of pharmaceutical technology as sanitary materials or implants, which make them an interesting support for drug delivery. Low pressure plasma allows modifying the first nanometers on the surface of polymers without altering their bulk properties. The aim of the present work was to evaluate the use of plasma technology as an efficient tool to modify polyamide 6.6 fibers and its relevance on the incorporation and release of an active principle, in this case caffeine, from the materials. Therefore, surface modification of polyamide 6.6 (PA 66) fiber properties (wettability, chemical, and topographical properties) was evaluated under different plasma working conditions. It was shown that the thickness of a PDMS coating layer on the fibers was reduced as a function of plasma working conditions (increased air flow rate), and that surface functionalization of polyamide took place by oxygen‐containing moieties without any degradation or alteration in fiber topography. In vitro caffeine release showed that plasma gas flow increase improves significantly (up to 90% after 24 h) the delivery of active principle from the fabrics without altering the release mechanism from the PA 66 fabrics.