BACKGROUND: This randomized clinical trial compares the outcomes of combination treatment by autogenous periosteal membranes and bone graft versus guided tissue regeneration (GTR) with collagen membranes or open-flap debridement (OFD) only in the treatment of intraosseous defects. METHODS: Forty-two patients affected by moderate to severe chronic periodontitis were enrolled. Each patient had one deep intrabony defect (≥6 mm). They were randomly assigned into three groups: patients treated with 1) an OFD procedure alone (OFD group); 2) a GTR procedure with collagen membranes (GTR group); and 3) a combined treatment procedure by autogenous periosteal membranes and autogenous bone chips (aCPRT group). Clinical and intrasurgical examinations including probing depth (PD), clinical attachment level (CAL), gingival recession (GR), and defect bone level (DBL) were performed at baseline and after 1 year. RESULTS: After 1 year, all of the evaluated clinical parameters showed statistically significant changes from baseline within each group (P <0.01). The GTR and aCPRT groups had significantly greater PD reductions (5.2 and 4.4 mm, respectively) and CAL (3.2 and 3.9 mm) and DBL gains (2.4 and 3.1 mm) compared to the OFD group (PD, 2.9 mm; CAL, 1.6 mm; DBL, 1.5 mm); moreover, the aCPRT group showed a significantly smaller GR increase (0.5 mm) and a greater DBL gain (3.1 mm) compared to the GTR group (2 and 2.4 mm, respectively; P <0.05). CONCLUSIONS: Both the GTR and aCPRT treatments produce additional clinical benefits over OFD alone. Moreover, the aCPRT technique can minimize post-surgical GR and produce better defect bone-level improvement.