It has long been questioned whether antibiotics, used as a supplement to traditional therapy, provide any lasting benefit in the treatment of chronic periodontitis. This study was designed to evaluate Spiramycin as an adjunct to scaling and root planing in the treatment of advanced chronic periodontitis. In total, 193 patients with advanced periodontitis were recruited in seven centres using selection criteria previously described. After undergoing thorough scaling and root planing, all patients randomly received either Spiramycin, 1,500,000 international units, twice per day (IU, bid) for 14 days (96 patients), or a visually-identical placebo capsule (97 patients). The clinical parameters measured were plaque index, crevicular fluid level, probing depths, bleeding on probing and attachment level changes. Data was recorded at baseline, two-, eight-, 12- and 24-weeks visits. A total of 189 patients completed the study (96 placebo, 93 Spiramycin). Statistically significant differences in probing depth, favoring Spiramycin, were seen at two weeks (p < 0.0125), eight weeks (p < 0.0020), 12 weeks (p < 0.0032) and 24 weeks (p < 0.0075). Spiramycin also produced a significant improvement in attachment level at 12 weeks (p < 0.0146). All other clinical parameters showed no difference between drug and placebo. This study shows that Spiramycin, as an adjunct to thorough scaling and root planing, provides a statistically significant improvement in probing depths for up to 24 weeks when compared with scaling and root planing alone. Both longer studies and microbiologic evaluations are necessary to determine whether a more lasting benefit is possible.