Purpose: C1-inhibitor (C1-INH) related hereditary angioedema (C1-INH-HAE) is a rare pathological condition caused by a deficiency or a functional alteration of serum protein C1-INH. Clinical manifestations are represented by recurrent, potentially life-threatening episodes of cutaneous or mucosal oedema. The present study analysed the effectiveness of a specific short-term prophylaxis protocol for the management of C1-INH-HAE patients requiring chronic periodontitis treatment. Materials and Methods: Ten consecutive C1-INH-HAE patients with mild to moderate chronic periodontitis were treated by non-surgical periodontal therapy with a full-mouth scaling approach (FMS) in two sessions 24 h apart. All patients underwent a short-term prophylaxis protocol of acute attacks based on the association of attenuated androgen (danazol), from 5 days before the first FMS session to 2 days after the second FMS session, and C1-INH concentrate given 1 h before the first FMS session. Patients were examined for periodontal changes over a 6-month period. Results: None of patients developed complications or oedema up to 1 week postoperatively. Compared to baseline, scaling and root planing (SRP) treatment yielded, at 6 months, a statistically significant improvement in probing depth (PD) (baseline: 5.24 mm ± 0.85 mm vs 6 months: 2.96 ± 0.31 mm), clinical attachment level (CAL) (baseline: 5.46 ± 0.81 vs 6 months: 3.89 ± 0.38 mm), full-mouth bleeding score (FMBS) (baseline: 27.6 ± 2.2% vs 6 months: 18.5 ± 2.1%) and in full-mouth plaque score (FMPS) (baseline: 28.6 ± 2.4% vs 6 months: 21.66 ± 3.3%). Conclusions: This study showed the clinical effectiveness of the reported prophylaxis protocol in preventing acute attacks in HAE patients requiring non-surgical periodontal treatment, with no complications up to 1 week after FMS. Keywords: chronic periodontitis, complement c1 inhibitor protein, dental scaling hereditary angioedema, periodontal debridement