Objective To identify the different clinical phenotypes of antiphospholipid syndrome (APS) by using cluster analysis and describe cumulative damage of disease clusters. Methods This retrospective study includes patients with APS (+/- systemic lupus erythematosus (SLE)). Two-step cluster analysis was applied by considering clinical data. Damage was calculated for all patients by applying damage index for APS (DIAPS). Results A total of 237 patients (198 females; median age of 43 years; median follow-up of 9.5 years) were classified into four clusters. Cluster 1 (n = 74) consisted of older patients with arterial-predominant thrombosis, livedo reticularis, and increased cardiovascular risk; cluster 2 (n = 70) of SLE+APS patients with thrombocytopenia and heart valve disease; cluster 3 (n = 59) of patients with venous-predominant thrombosis, less extra-criteria manifestations; and cluster 4 (n = 34) of patients with only pregnancy morbidity with lower frequency of extra-criteria features and cardiovascular risk. Patients with SLE+APS (n = 123) had the highest mean DIAPS. Regarding clusters, 1 and 2 had high cumulative damage. While cumulative survival rates of clusters did not differ, cluster 2 and 3 had lower survival rates at further years. There was no correlation between DIAPS and mortality. Conclusion SLE+APS patients with extra-criteria manifestations and older APS patients with arterial thrombosis and increased cardiovascular risk have higher cumulative damage. Effective treatment of SLE disease activity and control of cardiovascular risk may help to reduce cumulative damage in these patients.