OBJECTIVES: In football, on-field rehabilitation (OFR) is critical during injury recovery for a player's safe return to sports (RTS). The study aimed to evaluate the effectiveness of an OFR framework for RTS in injured male professional football players. TRIAL DESIGN: A prospective block-randomised controlled-parallel trial was conducted (level of evidence 1b). METHODS: Male professional football players (mean age, 26.3±3.6 years) from Greece diagnosed with an acute, lower limb musculoskeletal (MSK) injury (confirmed clinically and through imaging) participated in the study. During rehabilitation, the participants' OFR was guided by either the On-Field Rehabilitation (On FI.RE.) accelerated framework (experimental group) or a traditional OFR framework for a late injury recovery phase (comparison group). Between July 2021 and January 2022, 76 players were randomly allocated to the experimental group (n=38) and the comparison group (n=38). Participants were blinded during the study regarding intervention therapeutic protocols. The primary outcome measure was the effect of On FI.RE. framework on the time needed to return to team training (RTT) participation. The correlation between the time needed to return to on-field activity and RTT was calculated. Subsequent injuries were registered for a 12-month follow-up period. RESULTS: The intervention protocol, On FI.RE. framework, had a statistically significant effect on the time needed to RTT (F(1) = 49 626, p<0.001) with a large effect size (ES; η=0.422) and fewer days (mean=23.8±9.1 days) needed than the comparison group (mean=30.3±9.8 days). There was a strong correlation between return to on-field activity and the time needed to RTT (r = 0.901, p<0001) with a large ES (r>0.5). Six subsequent injuries were registered in the traditional OFR framework group, and one subsequent injury in the On FI.RE. framework group after a follow-up period of 12 months. CONCLUSION: The On FI.RE., an accelerated OFR framework during injury recovery, is more effective than a traditional OFR framework, reducing the time a player needs to RTS. It entails a very low risk of reinjury. TRIAL REGISTRATION NUMBER: NCT05163470.