OBJECTIVE: To evaluate the effect of early rehabilitation on therapeutic outcomes of patients in the ICU requiring mechanical ventilation. METHODS: Electronic databases up to June 15, 2024 were searched. Randomized controlled trials (RCTs) that compared early rehabilitation with standard rehabilitation for patients in the ICU on mechanical ventilation were included. The effects of early rehabilitation on outcomes such as duration of mechanical ventilation (days), ICU length of stay (days), hospital length of stay (days), ICU and in-hospital mortality, and ICU-acquired weakness (ICU-AW) were evaluated using a random-effects model. RESULTS: Nineteen RCTs met the inclusion criteria for this study, involving 3076 patients in the ICU on mechanical ventilation. Meta-analysis based on the random-effects model showed that early rehabilitation significantly reduced the duration of mechanical ventilation, ICU-AW risk, ICU length of stay, and total hospital length of stay. Analysis of the timing of early rehabilitation indicated that implementing early rehabilitation within ⩽48 or ⩽72 h after ICU admission or mechanical ventilation had varying effects on the duration of mechanical ventilation, ICU length of stay, and total hospital length of stay. CONCLUSION: Early rehabilitation can improve the therapeutic outcomes for ICU patients on mechanical ventilation. The optimal time for implementing early rehabilitation appears to be 48-72 h after ICU admission or initiation of mechanical ventilation, but further research is needed. CLINICAL TRIAL NUMBER: INPLASY202470068.