The aims of the study were to describe inpatient harm events detected via an automatic electronic trigger system (ETS) and to consider their financial consequences. Over a 27-month period, inpatient harm events were identified and documented in 1 healthcare system with 37 acute care facilities. Patients who experienced harm (all harm or preventable harm only) were compared with similar patients who did not. Clinical, financial, and demographic data were used to identify labor-adjusted direct variable costs (DVC) and potential differences in length of stay (LOS) associated with all-harm, preventable-harm, and nonharmed cohorts. Age-adjusted Charlson Comorbidity Index, case mix index, diagnosis-related groups, major diagnostic category, sex, age, location, diagnosis, adverse event category and subcategory, preventability, and harm severity were used to compare cohorts. Total harm events reported via the ETS and the health system's voluntary event reporting system were compared. Nearly 93,000 encounters for all-harm (n = 25,665) and nonharmed cohorts (n = 67,217) were compared by random sampling of diagnosis-related group-matched all-harm and nonharmed groups to ensure similar clinical conditions, as measured by Charlson Comorbidity Index and case mix index. Sampling (2 groups, n = 100 and n = 200) showed that increased LOS was associated with harm; yet other clinical comparators were similar across groups. the preventable-harm subcohort had longer LOS (10.7 versus 5.9 days) and higher DVC ($13,442 versus $8024) than the nonharmed cohort. Identification of harm events was nearly 6-fold higher with the ETS than with the voluntary event reporting system. Patients with preventable harm had increased LOS that was associated with higher DVC per preventable-harm encounter in a large US healthcare system.