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This study aims to determine the effects of transurethral polyacrylamide hydrogel injection in patients considered ineligible for midurethral sling surgery.In this prospective observational study, 81 patients received treatment with transurethral polyacrylamide hydrogel injection. Patients were considered ineligible for placement of a midurethral sling based on significant comorbidity (48%), 1 or more previously failed invasive treatments (16%), mixed urinary incontinence (27%), continuous incontinence (5%), or previous pelvic radiation therapy (4%). Longitudinal assessment of subjective treatment outcomes was performed using the validated Urinary Distress Inventory (UDI) and the Pelvic Floor Impact Questionnaire at baseline, 2, and 6 months. To deal with repeated measurements, mixed linear models were used to assess changes in the outcomes over time.There was a significant improvement in the overall UDI score from baseline to month 2 follow-up (FU) (P<0.001). No major differences between the month 2 and 6 FUs were observed. The largest difference in effect was observed for the irritative and stress subscales. Twenty-five patients (33%) requested a second injection at the month 2 FU visit. At month 6 FU, the UDI scores for patients having had only 1 injection were largely unchanged, whereas all UDI domains worsened further for patients having had a second injection at the month 2 visit. After the injection, there were 3 minor adverse events (3.7%) and no serious adverse events.In patients considered ineligible for midurethral sling surgery, transurethral injection with polyacrylamide hydrogel may alleviate urinary incontinence symptoms. Repeat injections did not improve outcomes in this complicated group of patients.