Background :Postoperative pillar pain (deep-seated wrist pain worsened by leaning on the heel of the hand) sometimes occurs after carpal tunnel release (CTR), leading to weakness in the hand and delayed return to work. Increased pain sensitivity has been found to be associated with worse symptoms and poorer treatment response in a number of chronic musculoskeletal conditions, but few studies have investigated the association of pain sensitization with pillar pain after CTR. Questions/purposes: (1) Is preoperative pain sensitization in patients with carpal tunnel syndrome (CTS) associated with increased severity of pillar pain after open CTR? (2) What other demographic, electrophysiological, or preoperative clinical characteristics are associated with pillar pain after CTR? Methods: Over a 35-month period, one surgeon performed 162 open carpal tunnel releases. Patients were eligible if they had sufficient cognitive and language function to provide informed consent and completed a self-reported questionnaire; they were not eligible if they had nerve entrapment other than CTR or if the surgery was covered by workers compensation insurance. Based on these criteria, 148 (91%) were approached for this study. Of those, 17 (9%) were lost to followup before 12 months, leaving 131 for analysis. Their mean age was 54 years (range, 32-78 years), and 81% (106 of 131) were women; 34% (45 of 131) had less than a high school education. We preoperatively measured pain sensitization by assessing the patients' pressure pain thresholds by stimulating pressure-induced pain in the pain-free volar forearm and administering a self-reported Pain Sensitivity Questionnaire minor subscale, an instrument that assesses pain intensity in daily life situations. We evaluated postoperative pillar pain using the “table test” (having the patient lean on a table with their weight on their hands placed on the table's edge with elbows straight) with an 11-point ordinal scale at 3, 6, and 12 months after their surgical procedures. We conducted bivariate and multivariable analyses to determine whether the patients' clinical, demographic, and pain sensitization factors were associated with their postoperative pillar pain severity after CTR. Results :After controlling for relevant confounding variables such as age, education level, and functional states, we found that increased pillar pain severity was associated with the pressure pain threshold (b = -1.02 [-1.43 to -0.61], partial R2 = 11%, p = 0.021) and Pain Sensitivity Questionnaire minor (b = 1.22 [0.73-1.71], partial R2 = 17%, p = 0.013) at 3 months, but by 6 months, only Pain Sensitivity Questionnaire minor (b = 0.92 [0.63-1.21], partial R2 = 13%, p = 0.018) remained an associated variable for pillar pain. Additionally, gender (women) was associated with increased pain severity at 3 (b = 0.78 [0.52-1.04], partial R2 = 9%, p = 0.023) and 6 months (b = 0.72 [0.41-1.01], partial R2 = 8%, p = 0.027). At 3 months, pressure pain threshold, Pain Sensitivity Questionnaire minor, and gender (women) collectively accounted for 37% of the variance in pillar pain severity; at 6 months, Pain Sensitivity Questionnaire minor and gender (women) accounted for 21% of the variance, but no relationship between those factors and pillar pain was observed at 12 months. Conclusions: Gender (women) and preoperative pain sensitization measured by pressure pain threshold and self-reported Pain Sensitivity Questionnaire were associated with pillar pain severity up to 3 and 6 months after CTR, respectively. However, the influence of pain sensitization on pillar pain was diminished at 6 months and it did not show persistent effects beyond 12 months. Pain sensitization seems to be more important in the context of recovery from surgical intervention (in the presence of a pain condition) than in healthy states, and clinicians should understand the role of pain sensitization in the postoperative management of CTS. Future research may be needed to determine if therapeutic interventions to reduce sensitization will decrease the risk of pillar pain. Level of Evidence: Level III, prognostic study.