Abstract Background The recurrence of angina after percutaneous coronary intervention affects 20–35% of patients with stable coronary artery disease; however, few data are available in the setting of ST-segment elevation myocardial infarction. We evaluated the relation between coronary microvascular obstruction and the recurrence of angina at follow-up. Methods We prospectively enrolled patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Microvascular obstruction was defined as thrombolysis in myocardial infarction flow less than 3 or 3 with myocardial blush grade less than 2. The primary endpoint was the recurrence of angina at follow-up. Moreover, angina status was evaluated by the Seattle angina questionnaire summary score (SAQSS). Therapy at follow-up and the occurrence of major adverse cardiovascular events were also collected. Results We enrolled 200 patients. Microvascular obstruction occurred in 52 (26%) of them. Follow-up (mean time 25.17±9.28 months) was performed in all patients. Recurrent angina occurred in 31 (15.5%) patients, with a higher prevalence in patients with microvascular obstruction compared with patients without microvascular obstruction (13 (25.0%) vs. 18 (12.2%), P=0.008). Accordingly, SAQSS was lower and the need for two or more anti-anginal drugs was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. At multiple linear regression analysis a history of previous acute coronary syndrome and the occurrence of microvascular obstruction were the only independent predictors of a worse SAQSS. Finally, the occurrence of major adverse cardiovascular events was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. Conclusions The recurrence of angina in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention is an important clinical issue. The occurrence of microvascular obstruction portends a worse angina status and is associated with the use of more anti-anginal drugs.