Using the tripartite model of perfectionism that accounts for combined characteristics of the Perfectionistic Strivings and Perfectionistic Concerns dimensions, this study explored the mediating role of self-compassion to explain differences between adaptive and maladaptive perfectionists in four psychological distress domains: depression, generalized anxiety, social anxiety, and academic distress. A sample of 3,112 university students were classified into adaptive, maladaptive, and nonperfectionists. Results of mediation analyses comparing adaptive and maladaptive perfectionists indicated that adaptive perfectionists reported significantly greater self-compassion and lower psychological distress levels in all four areas. Self-compassion significantly mediated the associations between perfectionist groups in all four domains. These findings were largely supported across various ethnic and international student groups in the analyses by subgroups. Furthermore, parallel mediation analyses demonstrated the unique contributions of individual self-compassion subscales as mediators. Implications for clinical practice, training, and future research are discussed.