BACKGROUND Nurses play an important role in detecting patients with clinical deterioration. However, the problem of nurses failing to trigger deteriorating ward patients still persists despite the implementation of a patient safety initiative, the Rapid Response System. A Web-based simulation was developed to enhance nurses' role in recognizing and responding to deteriorating patients. While studies have evaluated the effectiveness of the Web-based simulation on nurses' clinical performance in a simulated environment, no study has examined its impact on nurses' actual practice in the clinical setting. OBJECTIVE The objective of this study was to evaluate the impact of Web-based simulation on nurses' recognition of and response to deteriorating patients in clinical settings. The outcomes were measured across all levels of Kirkpatrick's 4-level evaluation model with clinical outcome on triggering rates of deteriorating patients as the primary outcome measure. METHODS A before-and-after study was conducted on two general wards at an acute care tertiary hospital over a 14-month period. All nurses from the two study wards who undertook the Web-based simulation as part of their continuing nursing education were invited to complete questionnaires at various time points to measure their motivational reaction, knowledge, and perceived transfer of learning. Clinical records on cases triggered by ward nurses from the two study wards were evaluated for frequency and types of triggers over a period of 6 months pre- and 6 months postintervention. RESULTS The number of deteriorating patients triggered by ward nurses in a medical general ward increased significantly (P<.001) from pre- (84/937, 8.96%) to postintervention (91/624, 14.58%). The nurses reported positively on the transfer of learning (mean 3.89, SD 0.49) from the Web-based simulation to clinical practice. A significant increase (P<.001) on knowledge posttest score from pretest score was also reported. The nurses also perceived positively their motivation (mean 3.78, SD 0.56) to engage in the Web-based simulation. CONCLUSIONS This study provides evidence on the effectiveness of Web-based simulation in improving nursing practice when recognizing and responding to deteriorating patients. This educational tool could be implemented by nurse educators worldwide to address the educational needs of a large group of hospital nurses responsible for patients in clinical deterioration.