The 20-item Pain Anxiety Symptom Scale (PASS-20) was adapted for Spanish-speaking Mexican Americans who report chronic pain (SSMACP). The instrument measures pain-related anxiety with fear, physiological, avoidance/escape, and cognitive anxiety as subtypes. In SSMACP, the Spanish PASS-20’s psychometric properties were evaluated while exploring relationships between pain-related anxiety with other variables. Using convenience sampling, 188 SSMACP (women = 108, men = 77; mean age = 37.20 years, standard deviation = 9.87) were recruited across the United States. Confirmatory factor analyses (CFAs) examined the structural validity of the hierarchical factor structure. Hierarchical multiple regression (HMR) examined incremental validity. Correlational analyses examined convergent validity. Cronbach’s coefficient alphas and McDonald’s omegas examined internal consistency. Pearson’s r, t tests, and analysis of variance tests examined relationships between demographic variables and PASS-20 scores. CFA supported the hierarchical factor structure (RMSEA =.061, SRMR =.038, CFI =.940). Total and subscale PASS-20 scores had acceptable convergent validity and internal consistency (range =.75 to.93). HMR found that total and subscale PASS-20 scores have adequate incremental validity, considering that they contributed uniquely to the prediction of generalized anxiety scores above and beyond other pain-related scores. Demographic variables were significantly related to total and subscale PASS-20 scores. Evidence supports the use of Spanish total and subscale PASS-20 scores in SSMACP. Exploratory evidence also informed on the possible consequences and predictors of their pain-related anxiety. The results also encourage pain research in specific populations from Latin America (e.g., Mexican Americans). PERSPECTIVE: The Spanish 20-item Pain Anxiety Symptom Scale has adequate psychometric properties in Spanish-speaking Mexican Americans who report chronic pain (SSMACP). This instrument can help catalyse pain research in SSMACP by informing on their pain-related anxiety and by helping evaluate other pain-related instruments. Evidence also informed on pain-related anxiety in SSMACP.