ObjectiveTo promote an effective strategy to improve the non-guideline-recommended prescribing (NGRP) of acid suppressive medications for stress ulcer prophylaxis (SUP) in critically ill patients and to evaluate the impact and barriers of a multifaceted intervention on NGRP in critically ill patients.Research design and methodsA retrospective, pre- post-intervention study was performed in the medical-surgical ICU. This study included pre-intervention and post-intervention period. There was no SUP guideline and intervention in the pre-intervention period. In the post-intervention period, the multifaceted intervention included five features: a practice guideline, an education campaign, medication review and recommendations, medication reconciliation, and pharmacist rounding with the ICU team.ResultsA total of 557 patients were studied (305 in the pre-intervention group and 252 in the post-intervention group). Patients who underwent surgery, stayed in ICU more than 7 days, or used corticosteroids experienced significantly higher rate of NGRP in the pre-intervention group. The average percentage of patient days of NGRP was significantly reduced from 44.2% to 23.5% (p < .001) by implementing the multifaceted intervention. The percentage of patients with NGRP decreased from 86.7% to 45.5% in terms of all 5 criteria (indication, dosage, IV to PO, duration, and ICU discharge; p = .003). Per-patient NGRP cost decreased from $45.1 (22.6, 93.0) to $11.3 (11.3, 45.1; p = .004). The main barrier influencing NGRP was the factors of the patient, including the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), the number of comorbidities, and undergoing surgery.ConclusionThe multifaceted intervention was effective in improving NGRP. Further studies are needed to confirm whether our strategy is cost-effective.