Purpose We aimed to assess the accuracy of home titration in estimating apnea hypopnea index (AHI) and optimal pressure values and to compare improvements in subjective daytime sleepiness, sleep quality and quality of life, along with 3-months treatment adherence of patients that received at-home versus in-laboratory auto-titrating positive airway pressure (APAP) titration. Materials and Methods In patients with a diagnosis of obstructive sleep apnea syndrome (OSAS), a study arm of laboratory attended APAP titration was compared with a study arm of home titration using an APAP device for three days. Subjective questionnaires were evaluated before and after 3 months of treatment. Results Fifty-three patients with newly diagnosed OSAS were enrolled. There was a significant positive correlation between PSG AHI and APAP AHI (r(s) = 0.43,P = 0.003) and the fixed pressure for the APAP arm was positively correlated with the APAP PSG arm of the study (r(s) = 0.71,P < 0.001). When the Bland-Altman graphs were compared, it was seen that the measurements obtained by the APAP AHI method were 0.3 units higher than the PSG AHI measurements, and that the mean of the measurement differences between the two methods was not different than 0 (P[H-0: Mean = 0] = 0.551). After 3 months of treatment, average nightly use was slightly higher in the APAP arm (P = 0.387). Conclusions The results indicate that both titration methods were not clinically inferior in terms of a fixed optimal pressure, residual events, 3-months treatment adherence and change in subjective sleepiness, sleep quality and quality of life after treatment.