We conducted a study of ultrasound (US)-guided pleural biopsy with a Tru-Cut needle and made a comparison with the results of a traditional pleural biopsy with an Abrams needle. A total of 49 patients with unilateral pleural effusion were included in this study. Twenty-four patients underwent a traditional pleural biopsy with an Abrams needle, and 25 patients underwent a US-guided pleural biopsy with a Tru-Cut needle. The age, sex, and underlying diseases in both groups were compatible. The amount of effusion was much less in the Tru-Cut group. In the patients who underwent the US-guided pleural biopsy with a Tru-Cut needle, the diagnostic sensitivity in pleural tuberculosis was 86 percent (6/7) and in pleural neoplasia it was 70 percent (7/10). In the patients who underwent traditional pleural biopsy with an Abrams needle, the diagnostic sensitivity in pleural tuberculosis was 20 percent (2/10) and in pleural neoplasia it was 44 percent (4/9). The result of US-guided pleural biopsy with a Tru-Cut needle was better than that of pleural biopsy with an Abrams needle, especially in pleural tuberculosis. No complication was found in the Tru-Cut group, but breakage and dislodgment of the tip of an Abrams needle occurred in one patient. The higher diagnostic yield in the Tru-Cut group may be attributed to the US guidance that can delineate the focal pleural abnormalities for biopsy. In conclusion, US-guided pleural biopsy by using a Tru-Cut needle was simple, safe, and well tolerated. It was particularly useful for patients with pleural tumor, thickened pleura, small amounts of pleural effusion, or loculated pleural effusion.