The increasing demand for more aesthetic/comfortable orthodontic alternatives fostered the utilization of clear aligners in recent years. However, the efficacy of clear aligners for treating complex malocclusions is often treated with scepticism. This case series aims to evaluate the predictability of the Invisalign® First system in moderate and severe cases requiring interceptive orthodontic treatments in mixed dentition. A total of 23 patients with 102 interceptive orthodontic malocclusion traits were selected for orthodontic treatment with Invisalign® First and were examined over 18 months (Phase 1). Clinical assessments included ClinCheck® predictions, cephalometric measurements, and measuring tools commonly used to quantify tooth movement. Measurements taken at the beginning and end of the treatment were compared. The complexity degree of each case was established based on the set of problems presented by each patient. All treatment objectives were achieved within 18 months, except for two Class II cases, with 69% of them solved with the first set of aligners. Additional aligners were used in the remaining cases. Even though these 23 cases suggest that the Invisalign® First (Phase 1) may be effective in most interceptive problems, controlled randomized clinical trials are required to evaluate movement predictability and how this relates to the problem complexity and additional aligners required.