Purpose To determine whether the use of one or two needles influences procedure performance and patient outcomes for ultrasonography (US)-guided percutaneous irrigation of calcific tendinopathy. Materials and Methods Institutional review board approval and written informed patient consent were obtained. From February 2012 to December 2014, 211 patients (77 men and 134 women; mean age, 41.6 years ± 11.6; range, 24-69 years) with painful calcific tendinopathy diagnosed at US were prospectively enrolled and randomized. Operators subjectively graded calcifications as hard, soft, or fluid according to their appearance at US. US-guided percutaneous irrigation of calcific tendinopathy (local anesthesia, needle lavage, intrabursal steroid injection) was performed in 100 patients by using the single-needle procedure and in 111 patients by using the double-needle procedure. Calcium dissolution was subjectively scored (easy = 1; intermediate = 2; difficult = 3). Procedure duration was recorded. Clinical evaluation was performed by using the Constant score up to 1 year after the procedure. The occurrence of postprocedural bursitis was recorded. Mann-Whitney U, χ2, and analysis of variance statistics were used. Results No difference in procedure duration was seen overall (P = .060). Procedure duration was shorter with the double-needle procedure in hard calcifications (P < .001) and with the single-needle procedure in fluid calcifications (P = .024). Ease of calcium dissolution was not different between single- and double-needle procedures, both overall and when considering calcification appearance (P > .089). No clinical differences were found (Constant scores for single-needle group: baseline, 55 ± 7; 1 month, 69 ± 7; 3 month, 90 ± 5; 1 year, 92 ± 4; double-needle group: 57 ± 6; 71 ± 9; 89 ± 7; 92 ± 4, respectively; P = .241). In the single-needle group, nine of 100 cases (9%) of postprocedural bursitis were seen, whereas four of 111 cases (3.6%) were seen in the double-needle group (P = .180). Conclusion The only difference between using the single- or double-needle procedure when performing US-guided percutaneous irrigation of calcific tendinopathy is procedure duration in hard and fluid calcifications. Clinical outcomes are similar up to 1 year. © RSNA, 2017.