Introduction and Hypothesis <p>The standard questionnaire for evaluated patients with bladder pain syndrome/interstitial cystitis (BPS/IC) is the O’Leary-Sant questionnaire, of which there is no validated Italian version. The objective of this study was to translate the O’Leary-Sant and validate it for Italian patients.</p> Methods <p>We enrolled BPS/IC patients (aged over 18&#xa0;years) alongside an age-matched control group without BPS/IC (healthy-volunteers). Inclusion criteria for BPS/IC patients: diagnosis of BPS/IC—according to the definition of the International Society for the study of bladder pain syndrome, ESSIC—and no specific treatment for BPS/IC. The study was approved by our institutional review board. We translated the questionnaire following the common guidelines for this process. All the enrolled women then answered the translated questionnaire at baseline and 2 weeks later. Statistics: Cronbach’s alpha; interclass correlation coefficient; Fisher–Freeman–Halton’s exact test or Student’s <i>t</i>-test when appropriate; Pearson’s r.</p> Results <p>Between February 2022 and March 2023, we enrolled 102 BPS/IC patients and 51 healthy volunteers controls. Data analysis demonstrated: internal consistency between the two versions of the questionnaire; reproducibility for total scores and all single items in both indexes of O’Leary-Sant; discriminatory ability of the questionnaire between patients’ mean scores and controls in both indexes and in single items; highly significant direct correlations between scores in the same domain and with the other domain (construct validity).</p> Conclusions <p>Our study demonstrates that our Italian version of the O’Leary-Sant questionnaire is a reliable, consistent, and valid instrument to evaluate symptoms of Italian speakers with BPS/IC.</p>