BACKGROUND: Anesthesiologists are responsible for optimizing patients' preoperative medications, including maximizing their compliance with preoperative medication instructions. The authors hypothesized that a standardized, simplified instruction sheet presented and verbally reinforced during the preanesthesia clinic visit would improve patient medication compliance on the day of surgery. METHODS: An unmatched case-control design was applied, with nonrandomized, preintervention (controls) and postintervention (cases) data collected. In the preintervention group, patient education/instruction regarding taking medications on the day of surgery continued in the existing, unstandardized manner. In the postintervention group, patients were given a simplified, multicolored Preoperative Patient Medication Instruction Sheet, which was consistently verbally reviewed with patients. Group differences and independent variable associations were analyzed with conventional inferential biostatistics. RESULTS: A total of 521 and 531 patients were enrolled in the preintervention group and postintervention group, respectively. Of this, 309 patients (60%) of preintervention group versus 391 patients (74%) of postintervention group (P < 0.001) were compliant with their preoperative medication instructions on the day of surgery. Use of the Preoperative Medication Instruction Sheet (adjusted odds ratio [aOR] = 1.83; P < 0.001), Caucasian race (aOR = 1.74; P = 0.007), and recalling receiving both verbal/written preoperative medication instructions (aOR = 1.51; P = 0.006) were associated with greater patient medication compliance. Older age (aOR = 0.67; P = 0.014) and higher American Society of Anesthesiologists status (aOR = 0.60; P = 0.004) were associated with lesser patient medication compliance. CONCLUSIONS: A standardized, multicolored, pictorial Preoperative Patient Medication Instruction Sheet, with patient communication in both verbal/written forms, seems to improve patient medication compliance on the day of surgery. African-Americans, older patients, and those with greater comorbidities may require a more concerted effort to achieve an adequate preoperative medication compliance. Copyright © 2014, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.