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Inconsistent and contradictory findings have appeared in the literature concerning the impact of body position on oxygenation in pleural effusion.We attempted to elucidate whether the size of the pleural effusion in patients with no parenchymal disease is the main determinant of posture-induced alterations in oxygenation parameters. We studied 62 spontaneously breathing patients aged 65.3±7.8 years (mean±SD), of whom 36 had large and massive-sized effusions (Group A) and 26 had small and moderate-sized effusions (Group B). Arterial blood gases were determined in four different body positions: sitting (SIT), supine (SUP), ipsilateral (IPS) and contralateral (CON) to the effusion side, after remaining relaxed for at least 20 min in each position. Separation into groups A and B was deliberately set from the position of the fluid meniscus line on a posteroanterior chest film just above the upper costal margin of the sixth anterior rib. A two-way ANOVA model with outcome variables PaO2, PaCO2 and [A–a] DO2 was used.In both groups the best oxygenation was found in SIT. The worst oxygenation (highest [A–a] DO2 value) occurred in group A in CON compared with IPS (59.4±7.6 vs 49.0±7.5 mm Hg, p<0.001) and in group B in IPS compared with CON (51.0±8.7 vs 39.5±9.2 mm Hg, p<0.001). Also, PaCO2 showed significant differences in both groups in IPS compared with CON (p=0.002).Patients with large-sized effusions exhibit the worst oxygenation when lying on the side contralateral to the effusion, while those with small-sized effusions exhibit the worst oxygenation when lying on the side ipsilateral to the effusion.