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Background: Of various explanations for the ‘obesity paradox’ that lean people with cardiovascular diseases are more likely to have poorer outcomes vs. obese, one hypothesis is that obese patients display a readily identifiable high vascular risk phenotype that may lead to receiving or seeking earlier/more aggressive treatment.Objective: To examine whether lean stroke patients are less likely to receive optimal combination treatment (OCT) and explore a differential impact of combination therapy on clinical outcomes in lean stroke patients.Methods: We analyzed a clinical trial dataset comprising 3643 recent (<120 days) ischemic stroke patients followed up for 2 years. Subjects were categorized as having lean body mass index (BMI, <25 kg/m2, n=1006), overweight BMI (25 to 29.9 kg/m2, n=1493), and obese BMI 30 Results: All-cause death occurred in 7.3% in lean, 5.5% in overweight, and 5.1% in obese patients. Frequency of OCT (level III) was 45.8% in lean, 51.7% in overweight, and 55.3% in obese patients. Subjects with lower BMI status had lesser frequency of OCT (45.8% in lean, 51.7% in overweight, and 55.3% in obese; P<0.001). Obese (vs. lean) patients were less likely to experience death (HR 0.70; 95% CI: 0.50–0.99, P=0.034), although this decreased risk was slightly attenuated and not significant after multivariable adjustment and was not seen with major vascular events. In multivariable analyses, compared with levels 0 and I, level II and level III were linked to lower risk of major vascular events (0.55; 0.32-0.95 and 0.48; 0.28–0.83) and death (0.44; 0.21-0.96 and 0.23; 0.10–0.54) among lean patients.Conclusions: OCT of secondary prevention medication after a recent ischemic stroke is less frequent in lean (vs. obese) patients, but when implemented is related to significantly better clinical outcomes among lean patients.