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Purpose: Obstructive sleep apnea (OSA) is the most commonly seen clinical sleep disorder. STOP-Bang, a widely used screening tool, yields a composite score based on eight dichotomized items including male gender. This study was designed to validate STOP-Bang among clinically referred patients and tested alternative scoring designs on tool performance, with a focus on gender differences in OSA., Method: STOP-Bang was administered to 403 female and 532 male subjects, followed by comprehensive sleep evaluation that included measurement of apnea-hypopnea indexes. Gender differences in STOP-Bang scores, OSA diagnosis, and severities were explored, and gender-specific alternative score cutoffs evaluated. Optimal operating points (OOP) were tested for female body mass index (BMI) and male neck circumference to inform STOP-Bang threshold refinement. Receiver operating characteristic curves were used to compare conventional and modified STOP-Bang., Results: STOP-Bang performance by gender showed extremely low specificity in males at the recommended cutoff of ≥3. Better utility was presented at a cutoff of 4 or 5 among clinically referred patients irrespective of gender differences. Screening performance was improved by modifying BMI and/or neck circumference thresholds using gender-triaged OOP estimation. Three gender-based model revisions outperformed conventional STOP-Bang., Conclusion: Our study suggests that gender-specific consideration needs to be incorporated into the application of STOP-Bang in a clinically referred patient population with a higher risk of OSA. Alternative scoring systems may improve predictive performance of STOP-Bang.