Randomized controlled trials (RCTs) have presented variable findings concerning the reduction of phosphorous level by nicotinamide. This systematic review is aimed to explore the safety and efficacy of nicotinamide in hemodialysis patients and was conducted by adhering to the PRISMA guidelines. Studies for inclusion were identified by running the suitable keywords in PubMed, Embase, and Cochrane Central till June 13, 2018. Cochrane risk of bias tool was used to judge the quality of the included RCTs. The primary outcome was change in serum phosphorus, calcium, and calcium-phosphorus product levels. Change in other biochemical parameters including serum calcium, parathormone, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for the risk of bias estimate. A total of 12 articles were qualified for inclusion in this study. All the included RCTs showed a statistically significant reduction in mean serum phosphorous and calcium-phosphorus product levels in the treatment arm as compared to the placebo group. Among several biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant difference. Flushing and diarrhea, followed by thrombocytopenia, were the most commonly reported adverse events in the treatment group. Nicotinamide was found to be effective in reducing the phosphorous level and calcium-phosphorus product level and increasing the HDL cholesterol level in dialysis patients. The safety profile was found to be satisfactory.