INTRODUCTION: 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. OBJECTIVE: 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. METHODOLOGY: 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. RESULTS: 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%. CONCLUSION: 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.