This study assesses the joint-specific sustained effect of collagenase clostridium histolyticum treatment of Dupuytren disease over a 5-year follow-up period. The study includes 107 consecutive treatments in patients with extension deficits greater than 20° affecting the metacarpophalangeal or proximal interphalangeal joints. Success was defined as no follow-up treatment due to relapse or maintained extension deficit less than 20°. The 5-year estimate of no follow-up treatment was 79% (95% CI: 64–88) for metacarpophalangeal and 49% (95% CI: 26–69) for proximal interphalangeal joints, which was a significant difference (log-rank test, p = 0.0044). For those who did not undergo re-treatment, a non-significant relapse was found for metacarpophalangeal joints and a 65% (34°, 95% CI: 24–46) relapse for proximal interphalangeal joints. We conclude that treating metacarpophalangeal joints with collagenase clostridium histolyticum is effective with acceptable recurrence rates. However, when treating proximal interphalangeal joints with collagenase clostridium histolyticum, patients should be informed of the high risk of recurrence and the greater chance of need for further treatment. Level of evidence: II.