This study examines the relationship between vacation behaviors and burnout among US physicians. It found that 59.6% of physicians took 15 or fewer vacation days per year, with 19.9% taking 5 or fewer days. Most physicians (70.4%) performed patient-related tasks while on vacation, with 33.1% working 30 minutes or more per day. Less than half of physicians reported having full electronic health record (EHR) inbox coverage while on vacation. Multivariable analysis showed that concerns about finding someone to cover clinical responsibilities and financial concerns were associated with lower likelihood of taking more than 3 weeks of vacation. Taking more than 3 weeks of vacation and having full EHR inbox coverage while on vacation were associated with lower rates of burnout, whereas spending 30 minutes or more on patient-related work per vacation day was associated with higher rates of burnout. The study also found that full EHR inbox coverage while on vacation was associated with higher professional fulfillment. These findings suggest that system-level efforts to ensure physicians take adequate vacation and have coverage for clinical responsibilities, including EHR inbox, may reduce physician burnout. The study highlights the importance of vacation for physician well-being and the need for institutional support to help physicians disconnect from work during vacation. It also notes that physicians who work more hours per week are more likely to experience burnout. The study concludes that institutional efforts to provide operational support and clinical coverage when physicians are on vacation should be pursued to mitigate burnout risk.This study examines the relationship between vacation behaviors and burnout among US physicians. It found that 59.6% of physicians took 15 or fewer vacation days per year, with 19.9% taking 5 or fewer days. Most physicians (70.4%) performed patient-related tasks while on vacation, with 33.1% working 30 minutes or more per day. Less than half of physicians reported having full electronic health record (EHR) inbox coverage while on vacation. Multivariable analysis showed that concerns about finding someone to cover clinical responsibilities and financial concerns were associated with lower likelihood of taking more than 3 weeks of vacation. Taking more than 3 weeks of vacation and having full EHR inbox coverage while on vacation were associated with lower rates of burnout, whereas spending 30 minutes or more on patient-related work per vacation day was associated with higher rates of burnout. The study also found that full EHR inbox coverage while on vacation was associated with higher professional fulfillment. These findings suggest that system-level efforts to ensure physicians take adequate vacation and have coverage for clinical responsibilities, including EHR inbox, may reduce physician burnout. The study highlights the importance of vacation for physician well-being and the need for institutional support to help physicians disconnect from work during vacation. It also notes that physicians who work more hours per week are more likely to experience burnout. The study concludes that institutional efforts to provide operational support and clinical coverage when physicians are on vacation should be pursued to mitigate burnout risk.