Background The interaction between smoking and the use of antiplatelet agents on the prognosis of vasospastic angina (VA) is rarely investigated. Methods VA-Korea is a nation-wide multi-center registry with prospective design (n = 1812). The primary endpoint was the composite occurrence of acute coronary syndrome (ACS), symptomatic arrhythmia, and cardiac death. Log-rank test and Cox proportional hazard model were for statistical analysis. Also, we conducted interaction analysis in both additive and multiplicative scales between smoking and antiplatelet agents among VA patients. For additive scale interaction, relative excess risk due to interaction (RERI) was calculated and for multiplicative scale interaction, the ratio of hazard ratio (HR) was calculated. All statistical analysis conducted by Stata Ver 16.1. Results Patients who were smoking and using antiplatelet agents had the highest incidence rate in the primary composite outcome. The incidence rate was 3.49 per 1,000 person-month (95% CI: 2.30-5.30, log-rank test for primary outcome p = 0.017) and HR of smoking and using antiplatelet agents was 1.66 (95%CI: 0.98-2.81). The adjusted RERI of smoking and using antiplatelet agents was 1.10 (p = 0.009), and the adjusted ratio of HR of smoking and using antiplatelet agents was 3.32 (p = 0.019). The current study observed the interaction between smoking and using antiplatelet agents in both additive and multiplicative scales. Conclusions Smoking was associated with higher rates of unfavorable clinical outcomes among VA patients taking antiplatelet agents. This suggested that VA patients, especially those using antiplatelet agents should quit smoking.