BACKGROUND: Portable oxygen devices simplify and facilitate patient therapy. This study was designed to compare S pO 2 and patient satisfaction with a portable oxygen concentrator or a combined system consisting of a fixed device with continuous-flow oxygen dispensation and a portable device with pulse dispensation for ambulation. METHODS: This crossover trial assessed 25 subjects with COPD (92% men, mean age of 72.2 ؎ 7.4 y, mean FEV 1 of 34.14 ؎ 12.51% of predicted) at 4 hospitals in Madrid. All subjects had previously used the combined system, consisting of a fixed oxygenation system and a portable system for ambulation, with 16 (64%) using stationary and portable concentrators and 9 (36%) using a stationary reservoir and portable liquid oxygen bag. Oxygenation settings at rest and while walking were determined at baseline. Subjects were maintained on the previous combined system for 1 week and then switched to the portable oxygen concentrator for 1 week. Mean S pO 2 over 24 h was calculated using the software in the oximeter, and compliance was monitored (Visionox). RESULTS: Low S pO 2 (< 90%) was significantly more frequent during use of the portable concentrator alone than with the combined system (37.1% vs 18.4%, P < .05). The portable system alone was preferred by 43% of subjects, and the combined system was preferred by 36%, whereas 21% were not sure. CONCLUSIONS: Subjects preferred using a single portable oxygenation system both at home and during ambulation. Portable systems alone, however, did not supply the same levels of oxygenation as the combination of fixed and portable systems. Before the widespread adoption of portable systems as a single device, additional studies are needed to determine best-practice protocols for adjustment of daytime and nighttime oxygenation settings. (ClinicalTrials.gov registration NCT02079753)