Purpose: This study was done to develop and evaluate a smartphone application for the medication confirmation of high-alert medications. Methods: A nonequivalent control group non-synchronized design was used for this study. Participants in the treatment group used the application for four weeks. Data were analyzed using descriptive analysis, x²-test, and t-test for the homogeneity of participants, and a paired t-test for effectiveness in each group with the SPSS 18.0. Results: Stability of medication administration was estimated by knowledge and certainty, ranged from a score of one to three. A correct answer with high certainty was coded as high stability, low certainty regardless of correct answer was coded as a moderate stability, and incorrect answers with high certainty were rated as low stability. There were no differences in ‘knowledge of high alert medication’, ‘Certainty of knowledge’, ‘stability of medication administration’, ‘confidence of single checking medication’, and ‘medication safety activities’ between the treatment group and the comparison group. The treatment group reported a greater difference between pretest and post-test in ‘certainty of medication knowledge’ (t=3.51, p=.001) than the comparison group. Conclusion: Smartphone application for medication confirmation of high-alert medications will provide an important platform for reducing medication errors risk.