Background: The purpose of this single-masked, randomized, controlled clinical trial was to evaluate the effects of boric acid irrigation as an adjunct to scaling and root planing (SRP) on clinical and microbiologic parameters and compare this method with chlorhexidine irrigation and SRP alone in patients with chronic periodontitis (CP). Methods: Forty-five systemically healthy patients with CP are included in this study. They were divided into three groups: 1) SRP + saline irrigation (C); 2) SRP + chlorhexidine irrigation (CHX); and 3) SRP + boric acid irrigation (B). To determine an ideal concentration of boric acid, a preclinical analysis was conducted. At baseline, 1 month, and 3 months after treatment, clinical measurements, including plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP), were performed, and subgingival plaque samples were taken. Quantitative analysis of Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf ), and Treponema denticola (Td) was performed using real-time polymerase chain reaction (PCR) procedures. Results: The concentration of boric acid is 0.75% in this study. All clinical parameters showed statistically significant reduction at all time points compared to baseline in all groups (P <0.001). Wholemouth PD and CAL reduction was similar in all groups at all time points after treatment (P >0.05). The PD and CAL reductions for moderately deep pockets (PD ≥5 and <7) were greater in the B group compared to other groups between baseline and 1 month (P <0.05). For deep pockets (PD ≥7), reductions were similar in the B and CHX groups (P >0.05). BOP (percentage) was significantly lower in the B group compared with the CHX and C groups in the first month after treatment (P <0.001). GI and PI scores were significantly lower in the B and CHX groups compared with the C group at all time points after treatment (P <0.05). The amounts of Pg, Tf, and Td were significantly reduced in all treatment groups after 1 month (P <0.05). No statistically significant differences were detected among the groups for microbiologic parameters at any time points after treatment (P >0.05). Conclusions: The results of this study suggest that boric acid could be an alternative to chlorhexidine, and it might be more favorable because boric acid was superior in whole-mouth BOP as well as PD and CAL reduction for moderate pockets in early time periods.