Objective: In this radiographic and microbiologic split-mouth clinical trial, efficacy of a diode laser as an adjunct to conventional scaling in the nonsurgical treatment of peri-implantitis was investigated. Background data: Eradication of pathogenic bacteria and infected sulcular epithelium presents a significant challenge in the nonsurgical treatment of peri-implantitis. Materials and methods: Ten patients (mean age, 55.1 years; SD, 11.4) with 48 two piece, rough-surface implants and diagnosed with peri-implantitis were recruited (NCT02362854). In addition to conventional scaling and debridement (control group), crevicular sulci and the corresponding surfaces of 24 random implants were lased by a diode laser running at 1.0 W power at the pulsed mode (λ, 810 nm; energy density, 3 J/cm²; time, 1 min; power density, 400 mW/cm2; energy, 1.5 J; and spot diameter, 1 mm); (laser group). Healing was assessed via periodontal indexes (baseline and after 1 and 6 months after the intervention), microbiologic specimens (baseline and after 1 month), and radiographs (baseline and after 6 months). Results: Baseline mean pocket depths (4.71, SD, 0.67; and 4.38, SD 0.42 mm) and marginal bone loss (2.71, SD 0.11; and 2.88, SD 0.18 mm) were similar (p = 0.09 and p = 0.12) between the control and laser groups, respectively. After 6 months, the laser group revealed higher marginal bone loss (2.79, SD 0.48) than the control groups (2.63, SD 0.53) (p < 0.0001). However, in both groups, the microbiota of the implants was found unchanged after 1 month. Conclusions: In this clinical trial, adjunct use of diode laser did not yield any additional positive influence on the peri-implant healing compared with conventional scaling alone.