Supplemental Digital Content is Available in the Text. The reliability and validity of International Pain Outcome questionnaire Spanish adaptation is confirmed in a large heterogeneous sample. Factor scores can be used as a global outcome analysis tool. Choosing perioperative suitable treatments requires reliable and valid outcome measurements. The International Pain Outcome (IPO) questionnaire has been widely used for quality improvement and research purposes within the PAIN-OUT network that has collected more than 550,000 data sets of postoperative patients in 200 hospitals worldwide. Our aim is to confirm psychometric properties of the Spanish version of the IPO questionnaire and its invariance by pain predictors. Sample included 4014 participants within a large age range, who underwent different surgical procedures. Confirmatory factor analysis (CFA) assessed internal structure, considering invariance by sex, age, procedure, smoking, obesity, affective disorder, and chronic pain. Incremental predictive validity of factor scores on question would have liked more pain treatment and opioid requirement was also estimated with logistic binary regression. Confirmatory factor analysis verified original structure in 3 factors measuring pain intensity and interference (F1), adverse effects (F2), and perceptions of care (F3), with good internal consistency. Multigroup CFA analysis confirmed invariance by assessed pain predictors. Good incremental predictive capacity to identify would have liked more pain treatment was achieved. Our study confirms the factor structure, supports reliability, and adds some evidence of convergent validity of the Spanish adaptation of the IPO questionnaire. The sum of scores in its main factors serves a global outcome analysis tool. Low scores in F1 and F2 with high scores in F3 would indicate optimal quality of care