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Aim or Purpose: Clark's Twin-Block (CTB) functional appliance is commonly used to treat mandibular deficiency in skeletal class II growing patients. This study was conducted to identify cephalometric predictors for favorable soft tissue profile outcomes with CTB appliance. Materials and Methods: Using pre- and post-functional lateral cephalograms of 50 subjects treated with CTB, profile silhouettes were evaluated by a panel of orthodontists to assess improvement using the Visual Analogue Scale (VAS). Subjects were divided into favorable and unfavorable groups on the basis of VAS scores. Independent sample t-test was used to compare cephalometric skeletal and soft tissue measurements between the groups. Predictors of favorable and unfavorable outcomes were identified using the logistic regression analysis. Results: Statistically significant differences in multiple pre-treatment values between favorable and unfavorable groups were observed. Multivariable logistic regression analysis found the decreased value of lower lip to E line (95% CI: 0.142, 0.800) and decreased pogonion to nasion perpendicular distance (95% CI: 1.05, 1.85) to be significantly associated with favorable soft tissue profile outcomes. Conclusions: Pre-treatment hypodivergent skeletal pattern, reduced ANB, reduced lower incisor to pogonion distance and soft tissue recumbency were identified as predictors of favorable soft tissue outcomes for CTB treatment in growing patients with mandibular retrognathism.