Metatarsalgia is a condition usually treated by physiotherapists. A selected but not very often prescribed method is the use of custom made orthotics. A standardized approach has been developed by the authors to produce custom-made orthotics using a combination of biomechanical measurements. The result is a highly customized orthotic which is adjusted to the patient comfort and medical needs. In the literature there is a paucity of data regarding the evaluation of such custom-made orthotics in the treatment of short and longer term metatarsalgia. The authors’ approach of producing custom-made orthotics for metatarsalgia has been evaluated in a previous study, with one year follow-up with very good results. Purpose: It is the aim of the present study to evaluate the patientś level of satisfaction, the functional improvement and the subjective ratings of improvement after 2 years’ time usage of custom-made orthotics for metatarsalgia. Methods: A sample of 50 patients (men = 12) suffering from metatarsalgia and treated with orthotics, were followed after 2 years’ time. All the patients had replaced their initial pair of orthotics after 12 months in average (range: 10–15 months) with a new pair based on the same standardized procedure and on a new set of biomechanical measurements. The standardized procedure included a kinetic and kinematic analysis, a 2D podoscan analysis (morphology of the foot) and clinical measurements (leg length, varus/valgus deformities, etc). All acquired data were inserted into a specially designed CAD-CAM software (EasyCad®) in order to produce the final customized orthotic. Both data acquisition and design of the electronic CAD-CAM insole were performed by the same expert clinician. Outcome measures were the patient's reported level of pain on a VAS scale (0–10), the area of painful symptoms measured in mm2, and the Foot Functional Index (FFI). The patients completed the same set of questionnaires initially and after 2-years of orthotics usage, together with a satisfaction questionnaire (SQ) on a 4-point likert scale (complete improvement, significant improvement, minimal improvement, no improvement/worsening). The paired t-test was employed both for the VAS and the FFI scores comparisons. Percentages were used to describe the satisfaction level of the patients and the level of change in the surface of the painful area. Results: Statistically significant differences were noted for the VAS values (mean ± SD, VASt1 = 7.1 ± 1.8, VASt2 = 2.2 ± 1.7, p < 0.001) and the FFI (total score) (FFIt1 = 48.0 ± 12.7, FFIt2 = 17.7 ± 6.6, p < 0.001). The areas of symptoms improved completely/resolved in 44% of the patients, the 33% reported at least a redus reported similar or larger (worse) painful areas. The patients reported a general satisfaction level of 85% (including the first two answers), 5% reported worsening of the symptoms and 10% minimal improvement. Conclusion(s): The standardized approach followed by the authors of manufacturing custom-made orthotics for metatarsalgia has been shown to produce good functional improvement, patients’ satisfaction and subjective ratings of improvement (pain, surface of the symptomatic areas) after 2 years of usage. Implications: It is recommended the implementation of similarly standardized biomechanical measurements in order to produce highly customized orthotics for the treatment of metatarsalgia.