Background: Medial tibial stress syndrome (MTSS) or Shin splints is exercise-induced lower leg pain along the distal posterior-medial aspect of tibia caused by repetitive loading stress during running and jumping. It is one of the most common lower leg sports injury. Cryotherapy is the most commonly used treatment during immediate care of athletic injuries and acute soft tissue injuries and is also included as part of RICE (rest, ice, compression and elevation). Cryotherapy is helpful in reducing swelling as well as it exerts analgesic effect. The external compression is also used during immediate care phase and it helps in decrease tissue temperature and prevent oedema formation. Cryotherapy in combination with intermittent pneumatic compression hypothetically help in reducing the physiologic effects of traumatic tissue damage which is based on the models of cryotherapy and static compression therapy. This study aims to establish the efficacy of cryo-compression on shin splints in female amateur marathon runners. Methods: A total 30 subjects diagnosed with shin splints were selected for study. Subjects received cryo-compression for reducing pain and swelling and exercises to strengthen the muscles. Each session was conducted for 45 minutes duration, 5 days per week for 4 weeks. Outcome measure used was Numerical Pain Rating Scale (NPRS), Goniometry for ROM and Manual muscle testing (MMT). Results: According to statistical analysis, the results of the study demonstrate that there was a significant effect of the use of cryo-compression on numerical pain rating scale (p<0.0001), range of motion (ankle plantarflexion, dorsiflexion, eversion and inversion) (p<0.0001), manual muscle testing – ankle plantarflexors (p=0.0028) and ankle dorsiflexors (p<0.0001) during the pre and post intervention assessment. Conclusion: The conducted study shows that efficacy of cryo-compression on shin splints in female amateur marathon runners is very effective in reducing pain, increasing range of motion (ROM) and strength of muscles along with other treatment program. KEYWORDS: Cryo-compression, shin splints, numerical pain rating scale (NPRS), range of motion, ankle plantarflexion, ankle dorsiflexion, ankle eversion, ankle inversion, manual muscle testing, ankle plantarflexors, ankle dorsiflexors.