BACKGROUND: Limited evidence informs whether pre-operative values of two-point discrimination (2PD) in patients with carpal tunnel syndrome predict response to surgery. QUESTIONS/PURPOSES: The primary aim of this study was to determine the predictive value of pre-operative 2PD scores on outcomes following carpal tunnel release (CTR). In particular, we sought to evaluate whether a clinically relevant 2PD threshold exists that can predict symptomatic response after surgery. METHODS: Patients who underwent CTR between 2014 and 2018 were retrospectively reviewed. Static 2PD scores in each digit, as well as Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Levine-Katz scores, were collected from pre- and post-operative records. Pearson correlation coefficients assessed the relationship between pre-operative 2PD, early post-operative 2PD, and patient-reported outcome scores. Poor 2PD was defined as 2PD greater than 10 mm. RESULTS: Eighty-nine hands in 73 patients with a mean follow-up of 1.8 years were analyzed. Mean pre- and post-operative 2PD was 7.2 mm and 6.4 mm, respectively, in the most affected digit when measurable. Twenty patients had poor 2PD scores pre-operatively and 14 post-operatively. There was a positive correlation between pre- and early post-operative 2PD scores but no correlation between pre-operative 2PD score and final post-operative functional scores. Only 30% of patients with poor pre-operative 2PD scores demonstrated improvement, compared with 69% of patients with measurable 2PD. CONCLUSION: We found that greater pre-operative 2PD scores predicted greater early post-operative 2PD scores but did not lead to worse functional outcome scores post-operatively. Patients with poor pre-operative 2PD scores were likely to demonstrate improvement in functional outcomes scores, while having less reliable improvement in 2PD after CTR. Patients with poor 2PD should be counseled that improvement of tactile perception is less predictable.