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This study analyzes the risk factors of unfavorable treatment outcomes in rifampicin-sensitive pulmonary tuberculosis (PTB) patients. Clinical data of 694 patients with rifampicin-sensitive PTB admitted to Quzhou Hospital Affiliated to Wenzhou Medical University from January 2020 to December 2021 were retrospectively analyzed. Univariate and multivariate logistic regression were used to analyze the related risk factors, and the predictive value was assessed using the receiver operating characteristic curve. Among 66 patients with unfavorable treatment outcomes, 42 died from non-tuberculosis causes, 16 died from tuberculosis, and 8 had failed treatment. Multivariate Logistic regression analysis showed that retreatment of PTB (odds ratio [OR] = 2.750, 95% confidence interval [CI] 1.253-6.033), chronic obstructive pulmonary disease (OR = 3.229, 95% CI 1.678-6.212), respiratory failure (OR = 7.388, 95% CI 2.420-22.560), elevated C-reactive protein (CRP) (OR = 1.006, 95% CI 1.000-1.011), hypoproteinemia (OR = 0.902, 95% CI 0.839-0.969), and low body mass index (BMI) (OR = 0.976, 95% CI 0.959-0.992) were independent risk factors for unfavorable treatment outcomes in rifampicin-sensitive PTB patients (P < .05); retreated of PTB (OR = 5.347, 95% CI 1.355-21.099), respiratory failure (OR = 17.046, 95% CI 3.080-94.354), hypoalbuminemia (OR = 0.795, 95% CI 0.702-0.902), and low BMI (OR = 0.748, 95% CI 0.584-0.959) were independent risk factors for poor prognosis in rifampicin-sensitive PTB patients (P < .05). The area under the curve of CRP, serum albumin, and BMI combined to predict unfavorable treatment outcomes in PTB patients was 0.798 (95% CI 0.749-0.847), with a sensitivity of 92.4% and specificity of 51.4%. The area under the curve of serum albumin and BMI combined to predict the prognosis of PTB patients was 0.923 (95% CI 0.862-0.984), with a sensitivity of 93.8% and a specificity of 89.3%. The low BMI, hypoproteinemia, elevated CRP level, comorbidities, and retreatment are risk factors for unfavorable treatment outcomes and poor prognosis in patients with rifampicin-sensitive PTB. Serum albumin and BMI were good indicators for evaluating unfavorable treatment responses in rifampicin-sensitive PTB patients, and their combination could improve the accuracy of prognostic assessment.