Purpose <p>The indication for orthodontic treatment in children and adolescents is based on severity of tooth and jaw malocclusions that lead to limitations in oral health-related quality of life (QoL). We have already shown how overbite and overjet deviations negatively affect QoL. However, few studies have investigated the influence of anterior crowding in the upper jaw on QoL.</p> Methods <p>We selected 734 children and adolescents aged 11–14&#xa0;years from a&#xa0;population-based longitudinal cohort study (LIFE Child). The data used in this study were retrospectively analyzed. Evaluable jaw models were available for 554 subjects in which we performed three orthodontic space analyses: (i)&#xa0;purely visual assessment of the crowding of the incisors in the upper jaw (VA), (ii)&#xa0;the Little index (LI), and (iii)&#xa0;the Lundström analysis (LA). Limitations in QoL were determined using the German version of the Child Perceptions Questionnaire (CPQ-G-11-14), taking into account the effects of age, gender, socioeconomic status (Winkler score), orthodontic treatment, oral hygiene, overbite/overjet, and dental caries (decayed, missing, filled teeth [DMFT] index) as possible influencing factors.</p> Results <p>The percentage of individuals with crowding in our cohort was 11% according to VA, 14.3% according to LI, and 7.3% according to the LA. Within the three analyses, the groups of individuals with crowding did not fully overlap. The CPQ score (subscales: “emotional and social well-being”) was significantly higher in subjects with crowding independent of the type of crowding analysis (<i>p</i> &lt; 0.05), gender, or socioeconomic status (multivariable linear regression analysis).</p> Conclusion <p>Children and adolescents with crowding had significantly more QoL impairments, especially related to emotional and social well-being. It is necessary to perform more than one crowding analysis in order to find more affected individuals with a&#xa0;reduced QoL due to crowding.</p>