BACKGROUND: Muscle injuries are common traumatic events in the clinical practice of the rehabilitation field. There is still a gap in the scientific literature on the effectiveness of physical agent modalities in the management of muscle injuries in athletes. OBJECTIVE: The aim of this study was to assess the effectiveness of cryo plus ultrasound therapy com-pared to diathermy in combination with high-intensity laser therapy (HILT) for pain relief in professional footballers with muscle injuries. METHODS: A case-control study was conducted on 31 professional footballers with a muscle injury of the lower limbs. Of these, 17 patients, assigned to a Group A (AG), were treated with HILT and cryoultrasound therapy; the remaining 14 patients, assigned to a Group B (BG), underwent HILT and diathermy. We assessed the extent of the pain, the size of the muscle injury, frequency of recurrence and number of days to recovery, at the time of recruitment, at the end of the rehabilitation and 3 months after the injury. RESULTS: Group A athletes had a greater benefit on pain (4.65 ± 0.61 vs 3.24 ± 0.63; p< 0.05) and muscle injury recurrence. The return to play in the athletes of group A took place 4.73 days earlier. CONCLUSION: HILT and cryo plus ultrasound therapy, in combination with therapeutic exercise, rep-resent a valid strategy in the treatment of muscle injuries in professional footballers.