The aim of the study was to assess the influence of four mandibular protrusion positions, at a constant vertical dimension, on obstructive sleep apnea (OSA). Seventeen OSA patients (49.2 +/- 8.5 years) received an adjustable mandibular advancement device (MAD). The patients underwent four polysomnographic recordings with their MAD in situ at, in random order, 0%, 25%, 50%, and 75% of the maximum protrusion. The mean apnea-hypopnea index (AHI) values of the patients differed significantly between the protrusion positions (P < 0.000). The 25% protrusion position resulted in a significant reduction of the AHI with respect to the 0% position, while in the 50% and 75% positions, even lower AHI values were found. The number of side effects was larger starting at the 50% protrusion position. We therefore recommend coming to a weighted compromise between efficacy and side effects by starting a MAD treatment in the 50% protrusion position.