The objective of this work was to compare the effects of antimicrobial photodynamic therapy (PDT), diode soft laser therapy (DSL), and thorough deep scaling and root planing (SRP) for treatment of residual pockets. Thirty-two subjects with a history of non-surgical treatment for chronic periodontitis were included. Residual pockets >4 mm and bleeding upon probing were debrided with an ultrasonic device and then subjected to either PDT, DSL, or SRP. Pocket probing depth (PPD), bleeding on probing (BOP), and gingival recession were monitored over 6 months. Counts of four microorganisms were determined by direct hybridization with RNA probes. PPD decreased from 5.6 ± 1.0 to 3.8 ± 1.1 in 6 months (p < 0.001), and BOP decreased from 100% to 52% (p < 0.01). The risk for a site to remain >4 mm with BOP depended on initial PPD (p = 0.036) and was higher if treated with DSL (p = 0.034). Frequencies of three microorganisms were significantly lower in PDT- and SRP-treated than in DSL-treated quadrants (p = 0.02) after 14 days, but not at months 2 and 6. All three treatments resulted in a significant clinical improvement. PDT and SRP suppressed Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola stronger, and resulted in fewer persisting pockets after 6 months, than DSL application.