Collagenase injection for Dupuytrens contracture is commonly administered without anesthesia. The authors studied the benefit of injecting local anesthesia before collagenase in reducing treatment-related pain. This prospective cohort study included 187 patients (mean age, 69 years; 80 percent men) at two orthopedic departments in Sweden. At one center, 161 consecutive patients scheduled for collagenase injection were assigned to two groups by alternating outpatient clinics; 78 received collagenase without local anesthesia using a modified method (injecting 0.80 mg in multiple spots in the cord) and 83 received local anesthesia injected in the proximal palm before collagenase. At the other center, 26 consecutive patients received collagenase using the standard method (0.58 mg injected in one spot) without local anesthesia. Immediately after the first injection (collagenase or local anesthesia), the patients rated the severity of injection-related pain on a visual analogue scale from 0 (no pain) to 10 (worst pain). Before finger manipulation 1 or 2 days after injection, the patients rated the pain experienced since injection. Mean score +/- SD for pain experienced during modified collagenase injection was 4.3 +/- 2.5 without local anesthesia and 2.3 +/- 1.7 during injection of local anesthesia (before collagenase) (age-and sex-adjusted mean difference, 2.1; 95 percent CI, 1.5 to 2.7; p amp;lt; 0.001). Mean pain score +/- SD during standard collagenase injection without local anesthesia was 4.8 +/- 1.8. Mean pain score +/- SD during the injection-manipulation interval was 2.9 +/- 1.9 in the group without local anesthesia and 2.9 +/- 2.3 in the local anesthesia group (p = 0.79). This study shows that local anesthesia significantly reduces the patients overall pain experience during collagenase treatment for Dupuytrens contracture.