Supplementation with high doses of vitamin D, known as mega-dose or "stoss therapy," refers to administering high doses of vitamin D by oral or intramuscular route in short periods of time. In this sense, conducting a review to organize this knowledge in a single article will generate a helpful instrument for researchers working in this area and for health professionals who use this therapeutic tool. To carry out a literature review on safety and efficacy (normalization of serum vitamin D level, and changes in the clinical picture) of vitamin D mega-dose use. This is a systematic review of the literature searching data through the electronic banks of PubMed, Scielo, and LILACS, using the following keywords: "vitamin D," "mega-dose," "stoss therapy," "cholecalciferol," in different combinations. CONSORT questionnaire was used to assess the quality of the included studies. Of the 59 articles screened for this review, 10 were included in the review, studying patients with rickets, osteoporosis, and critically ill patients. Two studies compared the exact dosage of vitamin D by different routes of administration, and three studies compared different doses by the same route. All others studied vitamin D mega-dose versus placebo. Adverse effects were observed through the presence of hypercalcemia/hypercalciuria. Serum vitamin D levels were normalized between 70 and 100% of patients, and adverse effects ranged between 1.9 and 18.5%. The study demonstrated that vitamin D mega-dose therapy is effective in normalizing serum vitamin levels, and the toxicity assessed through adverse effects was low, with no expressive clinical significance. Despite this, there is still a need for further studies in the area to confirm the results found.