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Aim To compare immediate surgery to scaling and root planing ( SRP) in the treatment of advanced periodontitis focusing on the prevalence of residual pockets after treatment and cost-effectiveness (1); to elucidate the adjunctive effects of azithromycin in a second-treatment phase (2) up to 36 months. Materials and Methods Thirty-nine patients (18 males, 21 females; mean age: 54.6) received oral hygiene instructions and were randomly allocated to surgery ( n = 19) or SRP ( n = 20). Patients with residual pockets (≥6 mm) at 6 months received re-debridement of these sites and systemic azithromycin. Clinical measurements were performed at 12, 24 and 36 months whereby residual pockets underwent re-debridement. Patients were evaluated in terms of clinical response parameters and cost-effectiveness. Chair-time was used to assess the financial impact of treatment. Results Only six patients in the surgery group required additional treatment at 6 months, whereas 14 patients in the SRP underwent this therapy. Both treatment arms were equally effective in terms of clinical outcome demonstrating <2% residual pockets at 36 months. Surgery imposed an extra 746 Euro on the patient up to 6 months compared to SRP. At 36 months, 69 Euro of this amount could be offset due to the lower need for re-treatment during maintenance phase. Conclusions Surgery was ultimately associated with a significantly lower need for re-treatment during supportive care, however, at significantly higher costs over the 3 years. [ABSTRACT FROM AUTHOR]