ABSTRACT: BACKGROUND:It is proposed that vitamin C administration can reduce disproportionate pain and stiffness after distal radius fracture; however, randomized trials that tested this hypothesis have had inconsistent results. QUESTIONS/PURPOSES:(1) Is administering vitamin C after distal radius fracture associated with better ROM, patient-reported upper extremity function, and pain scores? (2) What factors are associated with post-fracture finger stiffness and worse upper extremity function? METHODS:This is a double-blind, randomized, placebo-controlled, noncrossover study. Between August 2014 and July 2017, we approached 204 consecutive patients, of which 195 were eligible, and 134 chose to participate. Participants were randomized to receive once-daily 500 mg vitamin C (67 participants) or placebo (67 participants) within 2 weeks after distal radius fracture. All patients received usual care at the discretion of their surgeon. The mean age of participants was 49 ± 17 years, 99 patients (74%) were women, and 83 (62%) were treated nonoperatively. The primary outcome was the distance between the fingertip and distal palmar crease 6 weeks after fracture. This measure is easy to obtain and previously has been shown to correlate with aggregate ROM of all finger joints. The secondary outcomes were total active finger motion, total active thumb motion, upper extremity-specific limitations, and pain intensity.An a priori power analysis suggested 126 patients would provide 80% power to detect a difference of 2 cm (SD 4.0) fingertip distance to palmar crease with ? set at 0.05 using a two-tailed Student's t-test. Accounting for 5% lost to followup, we included 134 patients.All analyses were intention-to-treat. Ten participants of the intervention group and five of the placebo group were lost to followup. Their missing data were addressed by multiple imputation, after which we performed linear regression analysis for our outcome variables. RESULTS:Administration of vitamin C was not associated with ROM, function, or pain scores at 6 weeks (distance to palmar crease: ? -0.23; 95% CI -1.7 to 1.2; p = 0.754; finger ROM: ? 4.9; 95% CI, -40 to 50; p = 0.829; thumb ROM: ? 0.98; 95% CI, -18 to 20; p = 0.918, Patient-Reported Outcomes Measurement Information System [PROMIS] score: ? 0.32; 95% CI, -2.6 to 3.2; p = 0.828; pain score: ? -0.62; 95% CI, -0.62 to 0.89; p = 0.729) nor at 6 months (PROMIS score: ? -0.21; 95% CI, -3.7 to 3.3; p = 0.904; pain score: ? 0.31; 95% CI, -0.74 to 1.4; p = 0.559). At 6 weeks, we found that more finger stiffness was mildly associated with greater age (? -1.5; 95% CI, -2.8 to -0.083; p = 0.038). Thumb stiffness was mildly associated with greater age (? -0.72; 95% CI, -1.3 to -0.18; p = 0.009) and strongly associated with operative treatment (? -32; 95% CI, -50 to -13; p = 0.001). Greater pain interference was modestly associated with greater functional limitations at 6 weeks (? -0.32; 95% CI, -0.52 to -0.12; p = 0.002) and 6 months (? -0.36; 95% CI, -0.60 to -0.11; p = 0.004). CONCLUSIONS:Vitamin C does not seem to facilitate recovery after distal radius fracture, but amelioration of maladaptation to nociception (pain interference) merits greater attention. LEVEL OF EVIDENCE:Level I, therapeutic study.