Abstract Objectives Cigarette smoking is an established risk factor for autoimmune diseases. However, whether smoking plays a clear role in thrombotic APS (TAPS) has not been determined. We aimed to investigate the effects of smoking on the clinical characteristics and prognosis of TAPS. Methods This was a prospective cohort study from 2013 to 2022. During the study period, 297 patients were diagnosed with TAPS, including 82 smokers and 215 non-smokers. After propensity score matching, 57 smokers and 57 non-smokers matched by age and sex were analysed. Results Overall, smokers with TAPS had more cardiovascular risk factors than non-smokers, including hypertension (36.59% vs 14.42%, P < 0.001), obesity (15.85% vs 7.44%, P = 0.029), dyslipidaemia (64.63% vs 48.37%, P = 0.012) and hyperhomocysteinaemia (62.20% vs 36.28%, P < 0.001). Arterial thrombotic events were more common in smokers at diagnosis (62.20% vs 46.05%, P = 0.013), especially myocardial infarction, visceral thrombosis and peripheral vascular thrombosis. After matching, smokers showed balanced cardiovascular risk factors with non-smokers at baseline, but retained a higher prevalence of arterial thrombosis (59.65% vs 33.33%, P = 0.005), mainly distributed in cerebral vascular, cardiovascula and retinal vascular territories. During follow-up, smokers presented a tendency for more recurrent arterial thrombosis and less recurrent venous thrombosis. Smokers had significantly poorer outcomes for organ damage with higher Damage Index for APS score (median 2.00 vs 1.00, P = 0.008), especially in the cardiovascular (26.32% vs 3.51%, P = 0.001), gastrointestinal (15.79% vs 1.75%, P = 0.016) and ophthalmologic (10.53% vs 00.00%, P = 0.027) systems. Conclusion Smoking is related to increased arterial events and poor prognosis in TAPS patients. Patients with TAPS should be fully encouraged to avoid smoking.