Background Rheumatic mitral stenosis (MS) is a significant cause of valvular heart disease. Pulmonary artery systolic pressure (PASP) reflects the hemodynamic consequences of MS and is used to determine treatment strategies. However, PASP progression and expected outcomes in patients with moderately severe MS remain unclear. Purpose We aimed to examine the impact of progression rate of PASP in moderately severe MS. Methods A cohort of 866 consecutive patients with moderately severe rheumatic MS (1.0 cm2. Results Data-driven phenotyping identified two distinct trajectories based on PASP progression: a rapid progression group (N=38, 8.7%) and a slow progression group (N=398, 91.3%). Patients in the rapid progression group were older and had more comorbidities than patients in the slow progression group, including diabetes, and atrial fibrillation (all P<0.05). The initial mean diastolic pressure gradient and PASP were higher in the rapid progression group than in the slow progression group (6.2±2.4 mmHg vs. 5.1±2.0 mmHg, P=0.001, and 42.3±13.3 mmHg vs. 33.0±9.2 mmHg, P<0.001, respectively). During a mean follow-up of 7.0±3.0 years, the event-free survival rate was significantly lower in the rapid progression group than in the slow progression group (log-rank P<0.001). Rapid PASP progression was a significant risk factor for composite outcomes even after adjusting for comorbidities (hazard ratio: 3.08, 95% confidence interval (CI): 1.68–5.64, P<0.001). Multivariate regression analysis revealed that PASP>40 mmHg was independently associated with the probability of rapid progression group allocation (odds ratio: 4.95, 95% CI: 2.08–11.99, P<0.001). Conclusions Two groups with distinct patterns of PASP progression were identified. Rapid PASP progression was associated with a significantly higher risk of the composite outcomes. The main independent echocardiographic predictor for rapid progression group allocation was initial PASP>40 mmHg. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): This study was supported by a Severance Hospital Research fund for Clinical excellence (SHRC) (C-2020-0041) and a faculty research grant of Yonsei University College of Medicine (6-2020-0156).