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Iselin's disease is a common cause of foot pain in adolescent athletes. Despite recommendations for conservative treatment, no standard protocol exists for the optimal combination of immobilization and physiotherapy. This study aimed to compare the efficacy of a combined protocol (relative immobilization with early physiotherapy) versus strict rest on Return-to-Sport (RTS) time. In this prospective cohort study, 44 patients diagnosed with Iselin's disease (mean age: 12.1 ± 1.7 years) were assigned to two treatment groups. The first group (n=22) received a combined protocol including the use of a removable ankle brace or strapping for relative immobilization, coupled with a structured early physiotherapy program (focusing on pain-modulation modalities, gentle peroneal stretching, and proximal strengthening) initiated within the first week. The second group (n=22) was managed with strict rest (activity cessation) without formal physiotherapy or immobilization aids. The primary outcome was the time (in weeks) to full, pain-free return to the primary pre-injury sport. Secondary outcomes included pain scores (Visual Analog Scale - VAS) at 4 weeks and patient satisfaction at 3 months. The mean time to RTS was significantly shorter in the combined protocol group (5.8 ± 1.4 weeks) compared to the strict rest group (8.3 ± 2.1 weeks) (p < 0.001). At the 4-week follow-up, pain scores (VAS) were significantly lower in the combined group (1.2 ± 0.9 vs. 3.1 ± 1.5; p < 0.001). Patient satisfaction at 3 months was rated as "Very Satisfied" or "Satisfied" in 95% of the combined group versus 73% of the strict rest group. A structured combined treatment protocol integrating relative immobilization and early physiotherapy leads to a significantly faster return to sport and better short-term pain control compared to strict rest alone in adolescents with Iselin's disease. This protocol offers an effective and active management strategy, potentially reducing the burden of time away from athletic activities.