Purpose: To examine whether in-bed cycling assists critically ill adults to reduce acute muscle wasting, improve function and improve quality of life following a period of critical illness. Materials and methods: A single-centre, two-group, randomised controlled trial with blinded assessment of the primary outcome was conducted in a tertiary ICU. Critically ill patients expected to be mechanically ventilated for at least 48 h were randomised to 30 min daily in-bed cycling in addition to usual-care physiotherapy (n = 37) or usual-care physiotherapy (n = 37). The primary outcome was muscle atrophy of rectus femoris cross-sectional area (RFCSA) measured by ultrasound at Day 10 following study enrolment. Secondary outcomes included manual muscle strength, handgrip strength, ICU mobility score, six-minute walk test distance and health-related quality of life up to six-months following hospital admission. Results: Analysis included the 72 participants (mean age, 56-years; male, 68%) who completed the study. There were no significant between-group differences in muscle atrophy of RFCSA at Day 10 (mean difference 3.4, 95% CI -6.9% to 13.6%; p =.52), or for secondary outcomes (p-values ranged p =.11 to p =.95). Conclusions and relevance: In-bed cycling did not reduce muscle wasting in critically ill adults, but this study provides useful effect estimates for large-scale clinical trials.