The purpose of the present study was to evaluate the long-term biological and clinical effects of a controlled delivery system releasing tetracyclines during the healing of interproximal periodontal defects treated by the technique of guided tissue regeneration (GTR) using e-PTFE membranes.Fifteen patients, each with two comparable interproximal periodontal defects, underwent surgical treatment with e-PTFE membranes in conjunction with tetracycline fibres at the test site and e-PTFE membranes alone at the control site. Microbiological specimens were taken from each site treated at baseline (T0) and one year after surgery (T4). Plaque index (PI), gingival index (GI), pocket depth at probing (PD) and attachment level at probing (PAL) were recorded at baseline (T0) and one year after surgery (T4). The presence of selected pathogenic microbial species, Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi), Fusobacterium Nucleatum (Fn) and Actinobaccillus Actinomicetemcomitans (Aa), was investigated and these species were identified by cultural methods.No statistically significant difference in the level of periodontal pathogens was detected between the test and control sites at time T4. Likewise, no significant clinical difference between the test site and the control site was detected at time T4.The results suggest that tetracycline fibres used in conjunction with e-PTFE membranes do not provide and further clinical and microbiological improvement or effect the healing of periodontal defects one year after GTR treatment.