Nursing-sensitive events (NSEs) are common, accounting for up to 77% of adverse events in hospitalized patients (eg, fall-related harm, pressure ulcers, and health care-associated infections). NSEs lead to adverse patient outcomes and impose an economic burden on hospitals due to increased medical costs through a prolonged hospital stay and additional medical procedures. To reduce NSEs and ensure high-quality nursing care, appropriate nurse staffing levels are needed. Although the link between nurse staffing and NSEs has been described in many studies, appropriate nurse staffing levels are lacking. Existing studies describe constant staffing exposure at the unit or hospital level without assessing patient-level exposure to nurse staffing during the hospital stay. Few studies have assessed nurse staffing and patient outcomes using a single-center longitudinal design, with limited generalizability. There is a need for multicenter longitudinal studies with improved potential for generalizing the association between individual nurse staffing levels and NSEs. This study aimed (1) to determine the prevalence, preventability, type, and severity of NSEs; (2) to describe individual patient-level nurse staffing exposure across hospitals; (3) to assess the effect of nurse staffing on NSEs in patients; and (4) to identify thresholds of safe nurse staffing levels and test them against NSEs in hospitalized patients. This international multicenter study uses a longitudinal and observational research design; it involves 4 countries (Switzerland, Sweden, Germany, and Iran), with participation from 14 hospitals and 61 medical, surgery, and mixed units. The 16-week observation period will collect NSEs using systematic retrospective record reviews. A total of 3680 patient admissions will be reviewed, with 60 randomly selected admissions per unit. To be included, patients must have been hospitalized for at least 48 hours. Nurse staffing data (ie, the number of nurses and their education level) will be collected daily for each shift to assess the association between NSEs and individual nurse staffing levels. Additionally, hospital data (ie, type, teaching status, and ownership) and unit data (ie, service line and number of beds) will be collected. As of January 2024, the verification process for the plausibility and comprehensibility of patients' and nurse staffing data is underway across all 4 countries. Data analyses are planned to be completed by spring 2024, with the first results expected to be published in late 2024. This study will provide comprehensive information on NSEs, including their prevalence, preventability, type, and severity, across countries. Moreover, it seeks to enhance understanding of NSE mechanisms and the potential impact of nurse staffing on these events. We will evaluate within- and between-hospital variability to identify productive strategies to ensure safe nurse staffing levels, thereby reducing NSEs in hospitalized patients. The TAILR (Nursing-Sensitive Events and Their Association With Individual Nurse Staffing Levels) study will focus on the optimization of scarce staffing resources. DERR1-10.2196/56262.