Vitamin C is increasingly being used, and even high doses are considered safe. However, complications including hemolysis have been reported. We performed a systematic search from PubMed, Science Direct, and Google Scholar databases from January 1975 till July 31, 2021. Search terms used were “Vitamin C” OR “ascorbic acid” AND “haemolysis” OR “haemolytic anaemia.” Data regarding patient's demographics, outcomes and dose, duration, and form of vitamin C were extracted. Fourteen case reports matched the selected criteria, with age ranging from 3 weeks to 75 years with 78.6% being males. About 71.4% were diagnosed to have glucose-6-phosphate dehydrogenase (G6PD) deficiency but previous hemolysis was reported in only two patients, and 57.1% were prescribed vitamin C for nutritional supplementation. The dose ranged from 1 to 200 g/day with 57.1% receiving intravenous formulations. Half of these patients developed other complications including acute kidney injury (AKI), disseminated intravascular coagulation, oxalosis, and methemoglobinemia. About 78.6% developed complications within 3 days of starting vitamin C and only one death was reported. Vitamin C is generally a safe drug but it should be prescribed with caution and only when benefits outweigh the risks. Physicians should be aware of potential complications like severe hemolysis and AKI, especially when using high doses and in G6PD deficiency.