Purpose Adolescence is a time of change when suffering from a medical condition such as short stature can impact the emotional well-being of adolescents. Our objective was to study the adjustment of adolescents with short stature (SS), analyzing the factors influencing it. Method In this cross-sectional study, we evaluated 101 adolescents with SS from different hospitals in Valencia, Spain, using instruments validated for the sample: anxious and depressive symptomatology (as a diagnostic adjustment measure), psychopathology, self-esteem, physical self-concept, psychological well-being, and parenting styles. Descriptive analyses, t-tests for independent samples, Pearson correlations, hierarchical regressions, and fuzzy set qualitative comparative analysis models (fsQCA) were performed. Results Emotional (β = 0.44; p  = 0.001) and hyperactive (β = 0.20; p = 0.001) symptoms predicted anxiety, emotional symptomatology (β = 0.25; p = 0.022), self-esteem (β = − 0.37; p = 0.001), and promotion of autonomy (β = 0.30; p = 0.001) predicted depression, and hyperactivity (β = 0.45; p = 0.001), self-esteem (β = − 0.43; p = .001), and humor (β = − 0.36; p = 0.001) predicted emotional distress. The fsQCA results show that none of the variables is a necessary condition for anxiety, depression, or emotional distress. However, different combinations of these variables are sufficient conditions to explain 85% of the high levels of anxiety, 81% of the low levels, 62% of the high levels of depression, 64% of the low levels of depression, and 74% of the high levels of emotional distress and 61% of the low levels. The most important variables in the fsQCA models were symptomatology, self-esteem, and parental styles. Conclusion The patient’s family dynamics, self-esteem, and emotional difficulties were the most relevant factors in predicting adjustment.