This prospective observational study reports on diaphragm excursion, velocity of diaphragm contraction, and changes in pleural pressure that occur with thoracentesis. Twenty-eight patients with pleural effusion underwent therapeutic thoracentesis. Diaphragm excursion and velocity of diaphragm contraction were measured with M-mode ultrasonography of the affected hemidiaphragm. Pleural pressure was measured at each aliquot of 250 mL of fluid removal. Fluid removal was continued until no more fluid could be withdrawn, unless there was evidence of nonexpandable lung defined as a pleural elastance greater > 14.5 cm H2O/L and/or ipsilateral anterior chest discomfort. Twenty-three patients had expandable lung, and five patients had nonexpandable lung. Velocity of diaphragm contraction (mean ± SD) increased from 1.5 ± 0.4 cm/s to 2.8 ± 0.4 cm/s pre-thoracentesis and post-thoracentesis, respectively (CI, 0.93-1.61; P < .001) in subjects with expandable lung. Velocity of diaphragm contraction (mean ± SD) increased from 2.0 ± 0.4 cm/s to 2.3 ± 0.4 cm/s pre-thoracentesis and post-thoracentesis (P = .45) in subjects with nonexpandable lung. Diaphragm excursion was significantly increased in subjects with expandable lung at the end of thoracentesis; diaphragm excursion did not increase to a significant extent in patients with nonexpandable lung. The velocity of diaphragm contraction and diaphragm excursion increased in association with fluid removal with thoracentesis in patients with expandable lung, whereas it did not significantly change in patients with nonexpandable lung. This may derive from improvement in loading conditions of the diaphragm in patients with expandable lung related to its preload and length-tension characteristics.