The purpose of this 12-month randomized, controlled clinical trial was to evaluate the efficacy of a monotherapy protocol with the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for treatment of peri-implantitis. Twenty patients with 36 implants exhibiting probing pocket depths (PPDs) > 4 mm and evidence of radiographic bone loss (RBL) were randomly divided into two groups. The test group was treated with the Nd:YAG laser, and the control group was managed with mechanical debridement only. Peri-implant clinical parameters were recorded at baseline and at 12 months after treatment. PPD, RBL, and bleeding on probing showed improvements after 12 months in the test and control groups. The laser therapy provided additional benefits of greater reduction in PPDs and increased bone level with no adverse outcomes. The results demonstrated that laser therapy could be a valuable modality for the treatment of peri-implantitis.