OBJECTIVE To determine the frequency of new-onset symptoms of central venous stenosis (CVS) after percutaneous transluminal angioplasty (PTA) of a hemodialysis access-related stenosis in patients with previously asymptomatic CVS and to identify risk factors for this phenomenon. METHODS Retrospective review was performed of patients treated with PTA for an access-related stenosis (excluding central vein interventions) between 2001 and 2016 who returned within 3 months with symptoms of CVS (ie, "unmasking"): 39 patients met these criteria. A control group of 122 patients who had untreated asymptomatic CVS and did not experience unmasking was selected. Fistulograms were graded for degree of CVS. A total of 51% of the unmasked group was male, with an average age of 65 years; 57% of the control group was male, with an average age of 63 years. RESULTS The incidence of unmasking among patients with untreated asymptomatic CVS was 4.9%. A total of 90% of the unmasked group (35 of 39) had upper-arm access, compared with 77% of the control group (94 of 122; P = .017). A total of 28% of unmasked-group patients (11 of 39) underwent thrombectomy, vs 4% of controls (5 of 122; P < .0001). A total of 54% of unmasked-group patients (21 of 39) had significant brachiocephalic vein stenosis, vs 26% of controls (32 of 122; P = .001). A total of 8% of unmasked-group patients (3 of 39) had superior vena cava stenosis, vs none of the 122 controls (P = .01). A total of 64% of unmasked-group patients (25 of 39) had extensive collateral vessels, vs 24% of controls (29 of 122; P < .0001). CONCLUSIONS The incidence of unmasking of asymptomatic CVS is low. Prophylactic treatment of asymptomatic CVS therefore remains generally inadvisable. However, patients undergoing declotting with extensive collateral vessels might warrant treatment of asymptomatic CVS.