In patients with acute respiratory distress syndrome, low tidal volume ventilation (LTVV) was associated with acute respiratory distress syndrome in patients with mortality. For a study, researchers sought to look into the link between LTVV and mortality in COVID-19 patients. A secondary analysis of a national observational study in COVID-19 patients during the pandemic’s first wave. They compared COVID-19 patients who received LTVV, defined as controlled ventilation with a median tidal volume of less than or equal to 6 mL/kg predicted body weight over the first 4 calendar days of ventilation, to those who did not. The primary endpoint was mortality at 28-days. Furthermore, investigators identified factors associated with LTVV use. LTVV was administered to 294 (32.5%) of the 903 patients. The 2 patient groups had the same disease severity scores and ARDS classification. The primary endpoint, 28-day mortality, was met in 68 of 294 patients (23.1%) who received LTVV versus 193 of 609 (31.7%) who did not (P<0.001). LTVV was found to be related to 28-day mortality (HR, 0.68 (0.45 to 0.95); P=0.025). LTVV use was independently associated with age, height, initial tidal volume, and continuous muscle paralysis. Approximately one-third of the patients in this invasively ventilated COVID-19 cohort received LTVV. The use of LTVV was linked to a lower 28-day mortality rate. The use of LTVV was associated with potentially modifiable factors such as initial tidal volume and continuous muscle paralysis. The outcomes were significant because they might assist clinicians in identifying patients who were at risk of not receiving LTVV.