Objective: To study the value of an early (mechanical ventilation after 24 h) non-sedation protocol for intubated, mechanically ventilated patients in the respiratory intensive care unit (RICU). Methods: Seventy intubated, mechanically ventilated patients were prospectively enrolled and randomly assigned to management with early non-sedation (intervention group; n=35) or with daily interruption of sedation (DIS) (control group; n=35). The duration of mechanical ventilation, length of the RICU and hospital stay, RICU and hospital mortality, drug consumption, RICU and hospitalization expenses, incidence of complications and adverse events and serum levels of vital organ damage and inflammatory markers after mechanical ventilation for 48 h were recorded and compared. Results: Patients in the intervention group had a shorter duration of mechanical ventilation than those in the control group [(7±5) vs (11±9) d, P<0.05] and were discharged from the RICU [(9±7) vs (18±9) d, P<0.05] and hospital earlier [(17±14) vs (29±22) d, P<0.05] than those in the control group. The doses of midazolam were significantly lower in the intervention group than in the control group [(99±104) vs (482±337) mg, P<0.05]. The RICU and hospitalization expenses were both significantly lower in the intervention group than in the control group [53(84) vs 88(173), 72(195) vs 154(234) thousand CHY, P<0.05]. In the intervention group, the occurrence rates of ventilator associated pneumonia (23% vs 46%), tracheotomy (14% vs 37%) and gastrointestinal adverse reactions (17% vs 40%) were significantly lower than those in the control group (P<0.05). No differences were recorded in RICU and hospital mortality (P>0.05). The occurrence rates of unplanned extubation and reintubation and the need for CT brain scans were similar in the 2 groups (P>0.05). The levels of cardiac, liver and renal damage markers, lactic acid and C-reactive protein were the same in both groups (P>0.05). Conclusions: The early non-sedation protocol decreased the duration of mechanical ventilation and the length of stay in the RICU and hospital, and it did not increase the incidence of complications and adverse events.