Objective: In this article, efficacy of minimally-invasive outpatient laser-assisted uvulopalatoplasty (LAUP) procedure (NightLase Ò LAUP) to reduce apnea-hypopnea index (AHI) in patients with obstructive sleep apnea (OSA) is evaluated. Background: OSA is a serious condition, but its treatment is often not effective or is poorly accepted by patients. Newer modes of therapy that are more effective and also more accepted by patients need to be developed. The latest treatment approaches involve a minimally-invasive LAUP procedure. This procedure involves thermal processing of the relaxed soft palate and surrounding tissues using neodimium-doped yttrium aluminum garnet (Nd:YAG) and erbium-doped yttrium aluminum garnet (Er:YAG) lasers, resulting in favorable collagen shrinkage and development of new collagen fibers. Procedure has previously been reported to safely and effectively reduce snoring, as well as increase the volume of the oropharyngeal airway, and is well accepted by patients. Materials and methods: The efficacy of the minimally invasive LAUP procedure, combining Nd:YAG laser (k = 1064 nm) and Er:YAG laser (k = 2940 nm) applied to the soft palate for treatment of OSA on 27 patients with different severities of OSA was evaluated based on AHI measurements before and after only three 20-min sessions in an outpatient setting over a period of 45-60 days. Results: A decrease in AHI for all the patients with different severities of OSA tested in this study was achieved, with 66.3% average improvement (32-100%). Fifty percent or more improvement was achieved in 78% (21) of all patients. Conclusions: Based on our observations, the NightLase Ò LAUP treatment of OSA represents an effective and safe therapeutic method. Further research and longer term prospective trials are needed to improve the evidence base for the potential integration of this treatment method into the current guidelines for treatment of OSA.