Aim: To examine the effectiveness of the implementation of a clinical practice guideline on nurses screening patients for alcohol and other substance use, providing brief interventions, and referring patients at risk for treatment. Method: Medical record audits were conducted in selected medical and surgical wards of two metropolitan hospitals in Sydney prior to and three months following the guideline implementation. Result: Seventy-nine (pre) and 84 (post) patient records were audited. There were no differences in screening rates for alcohol (28% and 29%), tobacco (29% and 23%) and illicit drug use (16% and 8%) before and after implementation of the guideline. Practice implication: Factors which may have limited the effectiveness of the clinical practice guideline dissemination included design of the education program, existing level of nurses' knowledge and competence, and strategies in place to ensure sustainability of the program. We also provided suggestions for improvement of screening for alcohol and other substance use.