Objective: To investigate the impact on microbiologic variables of full-mouth scaling (FMS) and conventional scaling and root planing (cSRP) after 12 months. Method and Materials: In a prospective randomized controlled clinical study, 37 volunteers with moderate chronic periodontitis were treated by FMS or by cSRP in two sessions at 4-week intervals. Clinical attachment level, probing depth, and bleeding on probing were recorded at baseline as well as at 6 and 12 months. Four subgingival plaque samples were taken from the deepest sites in premolars and molars at baseline and after 12 months. Pooled sample analysis was performed using real-time polymerase chain reaction for the identification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Results: At baseline, the bacterial load of A actinomycetemcomitans was significantly higher in the cSRP group compared to the FMS group (P = .042). In the cSRP group, this load decreased significantly (P = .011), leading to similar quantities of A actinomycetemcomitans in both groups. Further, significant reductions in frequency were found in the FMS group for T forsythia and P gingivalis and in the cSRP group for A actinomycetemcomitans and T denticola. Conclusion: The data suggest that both therapy modalities lead to similar effects on target periodontal pathogen species. FMS compared to cSRP was not favorable in reduction of periodontopathogens. Keywords: microbiologic analysis, nonsurgical therapy, periodontal disease, randomized clinical trial