Abstract Background. Efficacy of professional mechanical plaque removal and subgingival instrumentation, performed to control periodontal diseases, is widely documented in literature. The goal of periodontal therapy is to control and or to eliminate the pathogens contained in periodontal pockets. Objective of the study. The aim of this randomized clinical study was to compare the clinical outcomes obtained with subgingival intrumentation after conventional quadrant-wise versus full-mouth scaling and to highlight the factors that determine which protocol to use. Materials and methods. 34 patients affected by periodontitis were randomly allocated to receive FM-SRP or Q-SRP. Periodontal and sociodemographic characteristics were collected at baseline and at 2 months after therapy. The primary outcome variable was PD reduction, while the secondary outcome variables were changes in clinical attachment level (CAL), bleeding on probing (BOP) and plaque index (PI). Results. A total of 34 patients were included without drop-outs. Mean age was 51.3 ± 11.2 years. Both groups showed statistically significant improvements in periodontal clinical parameters (p< 0.05). Non-surgical periodontal treatment was equally clinically effective at 2 months follow up (p0.05). Conclusion. Non-surgical periodontal therapy performed with combination of hand and sonic/ultrasonic instruments is an efficacious means to achieve infection control in periodontitis patients irrespective of the mode of delivery. Factors such as systemic diseases, behavioral problems, logistics, and the spread of periodontal disease have to be taken into account when choosing the protocol of treatment. Keywords: non-surgical treatment, periodontitis, scaling and root planning, subgingival instrumentation.