Aim: This multi‐centre, prospective, controlled trial was designed to examine the biological response of the matrix metalloproteinase(MMP) inhibitor subantimicrobial dose doxycycline (SDD) combined with access flap surgery on periodontal wound repair in patients with chronic severe periodontitis.

Material and Methods: Seventy subjects were enrolled into a 12‐month, randomized, placebo‐controlled, double‐masked trial to evaluate disease response to 6 months therapy and “wash‐out” of either placebo+surgery or SDD (20 mg b.i.d.)+surgery. Primary outcome measure included clinical attachment levels (CAL) and secondary outcomes included probing depth (PD), bleeding on probing (BOP), as well as gingival crevicular fluid bone marker assessment [collagen telopeptides (ICTP)]. These measurements were taken at baseline through 12 months post‐surgery and drug administration.

Results: Patients treated with SDD and surgery demonstrated stronger reductions in PD in surgically‐treated sites of 7 mm as well as gains in CAL (p<0.004). Furthermore, SDD+surgery resulted in short‐term reductions in ICTP levels compared with placebo. Rebounds in ICTP levels and clinical parameters occurred when SDD was withdrawn.

Conclusions: The results from this multi‐centre study suggests that SDD in combination with surgery improves the short‐term response of periodontal therapy by reducing PD, increasing CAL gain and inhibiting early stage bone resorption.