The first 3 questions of the Alcohol Use Disorders Identification Test (AUDIT-C) are often used as a brief alcohol screening instrument. However, the implications of common modifications made to the original AUDIT questions and response options have not been considered. The authors examined existing data from a randomized controlled trial of 310 persons with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) that was testing the efficacy of 2 antiretroviral medication adherence interventions. Logistic regression was used to model the probability of participants having inconsistent AUDIT-C item responses. Three patterns of conflicting responses to the AUDIT-C items were identified. Common item modifications resulted in 14% (n = 48) of the parent study sample reporting conflicting responses across related AUDIT-C items. The odds of having conflicting data were 3 times greater in opioid users (odds ratio [OR] = 3.139, 95% confidence interval [CI] = 1.267-7.777, P = .01) and greater in persons with higher levels of conscientiousness (OR = 1.053, 95% CI = 1.006-1.103, P = .03). Inconsistent question format and response options may impede proper scoring and interpretation of the AUDIT-C. Further discussion and consensus building are needed on the psychometrically ideal version of the AUDIT-C.