Background Comfort during colonoscopy is a critical component of safety and quality. Objective To develop and validate the Nurse-Assessed Patient Comfort Score (NAPCOMS). Design Prospective scale validation. Setting Colorectal cancer screening centers in the United Kingdom and Canada. Patients A total of 300 consecutive patients undergoing colonoscopy at participating colorectal cancer screening centers. Intervention The NAPCOMS was developed by using a modified Delphi process. During colonoscopy, two endoscopy room nurses independently observed and rated patient comfort and tolerability by using NAPCOMS. In addition, endoscopists reported global comfort scores and patients' reported global comfort by using visual 4-point Likert and National Health Service-United Kingdom Global Rating Scales. Main Outcome Measurements Reliability and validity of NAPCOMS was measured by using intraclass correlations (ICC) between nurse ratings of colonoscopies and between NAPCOMS, endoscopist ratings, and patient ratings of global comfort. Results The ICC for the overall NAPCOMS was 0.84 (95% confidence interval CI, 0.80-0.87). There was high agreement between the NAPCOMS and endoscopist ratings of comfort (ICC = 0.77; 95% CI, 0.72-0.81), moderate agreement between the NAPCOMS and patient ratings (ICC = 0.61; 95% CI, 0.53-0.67), and moderate agreement between the endoscopist and patient ratings (ICC = 0.52; 95% CI, 0.43-0.60). Limitations NAPCOMS was validated in outpatients who received colonoscopy with minimal to moderate sedation as part of a screening and surveillance program, so performance among inpatients or those requiring deep sedation was not tested. Conclusion NAPCOMS is a reliable and valid tool for assessing patient comfort in the setting of outpatient colonoscopy performed with minimal to moderate sedation.