Purpose: Full-mouth disinfection enables to reduce the probability of cross contamination from untreated pockets to treated ones, for completing the entire SRP under local anesthesia with chlorhexidine as a mouth wash in two visits within 24 hours. This study aimed to compare the clinical effects of modified full-mouth disinfection (Fdis) after 6 months with those of conventional SRP (cSRP). Methods: Thirty non-smoking chronic periodontitis subjects were randomly allocated two groups. The Fdis group underwent the entire SRP under local anesthesia in two visits within 24 hours, a week after receiving supragingival scaling. A chlorhexidine (0.1%) solution was used for rinsing and subgingival irrigation for Fdis. The cSRP group received SRP per quadrant under local anesthesia at one-week intervals, one week after they had received scaling. Clinical parameters were recorded at baseline, after 1, 3 and 6 months. Results: There are significant (P<0.05) decreases in the sulcus bleeding index, and plaque index, and the increases in gingival recession were significantly smaller with Fdis after six months compared with cSRP. There was significant improvement in the probing depth and clinical attachment level for initially medium-deep pockets (4-6mm) after Fdis compared with cSRP. Multi-rooted teeth showed significantly larger attachment gain up to six months after Fdis. Single-rooted teeth showed significantly more attachment gain, 1 and 6 months after Fdis. Conclusions: Fdis has more beneficial effects on reducing gingival inflammation, plaque level, probing depth, gingival recession and improving clinical attachment level over cSRP.