The performance of standard screening instruments and alternate measures against ICD-10 (International Classification of Diseases, 10th revision) and DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th revision) criteria for alcohol dependence and separately for harmful drinking/abuse were compared between probability samples of 1511 emergency room (ER) patients from three hospitals in Pachuca, Mexico, and 586 Mexican-American ER patients in Santa Clara County, California. Sensitivity was highest for the Alcohol Use Disorders Identification Test (AUDIT), TWEAK, and Rapid Alcohol Problems Screen (RAPS) for alcohol dependence; sensitivity was highest for holding five or more drinks for harmful drinking/abuse in both samples. All instruments performed better for alcohol dependence than for abuse/harmful drinking. Arrests for drinking and driving performed better in Santa Clara than in Pachuca, while a positive Breathalyzer reading and reporting drinking prior to the event performed better in Pachuca; both were significantly more sensitive among the injured compared to the noninjured in Pachuca. The data suggest that instrument performance may be similar between those in Pachuca and those in the low acculturation group in Santa Clara, relative to those scoring higher on acculturation. While standard screening instruments appear to work reasonably well in both samples for alcohol dependence, variation across gender, injury, and acculturation subgroups suggests attention should be given to choosing the "best" instrument.