Ten patients with a diagnosis of generalized chronic periodontitis underwent nonsurgical periodontal therapy performed with the exclusive use of ultrasonic instrumentation and air polishing with erythritol powder. For each patient, four pockets with probing depths (PDs) of 4 to 10 mm were selected as experimental sites, and air polishing was performed either before (Group A) or after (Group B) ultrasonic scaling. PDs and clinical attachment levels significantly improved over a 12-month observation period. No significant difference was observed between the use of air polishing before or after ultrasonic instrumentation. The present clinical protocols could represent a suitable treatment for cause-related periodontal therapy.