High sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) are associated with vascular inflammatory responses and confirmed to be associated with cardiovascular disease and metabolic syndrome. However, it is still unclear whether the combination of hs-CRP and Hcy predicts the development of metabolic syndrome. This study evaluated the combination of hs-CRP and Hcy as a predictor of metabolic syndrome in healthy adults. From January 2017 to August 2019, this study was conducted on healthy adults who were over 20 years old. They underwent a general health examination at a general hospital in the Seoul metropolitan area. High hs-CRP and Hcy levels were defined as outcome values corresponding to the 75th percentile of all the subjects. The diagnosis of metabolic syndrome applied the NCEP-ATP III criteria. hs-CRP increased the risk of developing metabolic syndrome in the fourth quartile more than in the first quartile. The probability of developing metabolic syndrome in the group with only high hs-CRP levels was 2.38 for men and 3.50 for women. The incidence of metabolic syndrome with a combination of both high hs-CRP and Hcy levels was 3.42 for men and 6.55 for women. In conclusion, this study demonstrated that the combination of high levels of serum hs-CRP and Hcy can be a predicting factor for a patient’s risk of developing metabolic syndrome.