Introduction Vitiligo is an acquired pigmentary disorder clinically manifested by circumscribed depigmented macules and often associated with leucotrichia. Not much is known about the biochemical abnormality occurring in vitiligo. Our study aims to determine whether serum homocysteine is raised in vitiligo patients and whether it can be used as a prognostic marker for vitiligo. Material and methods This study is a hospital-based, case-control, analytical study conducted on 70 patients of vitiligo patients. A total of 30 staff of the hospital served as control. Venous blood was withdrawn from the antecubital vein from all study participants using all aseptic precautions. Investigation of blood homocysteine levels was done in all the study participants. Scoring of vitiligo was done based on Vitiligo European Task Force (VETF) criteria which take into account body surface area, stage, and spread. Results Mean serum homocysteine level among vitiligo patients was 14.40± 5.80 micromoles/lit as compared to 10.33± 5.05 micromole/lit in control groups, and this difference was statistically significant (t-value = 3.19and p-value = 0.002). The correlation coefficient was statistically significant (correlation coefficient = 0.25 and p-value = 0.03) in between homocysteine level and stage of the disease. On multiple comparisons difference in serum homocysteine level of progressing category is significantly raised as compared to control, stable, and regressing categories. Conclusion The mean serum homocysteine level among all vitiligo patients was higher as compared to control groups. Moreover, the serum homocysteine level of active cases is significantly higher as compared to control, stable, and regressing categories. Also, serum homocysteine levels showed a positive correlation with the degree of depigmentation, i.e., stage of the disease.