Advances in understanding of the perfectionism construct have been limited by an almost exclusive reliance on a variable-centered approach. This study utilized a person-oriented approach to examine Hewitt and Flett's conceptualization of multidimensional perfectionism in relation to health and well-being. Levels of conscientiousness, extraversion, and neuroticism were also assessed. Cluster analyses were employed to examine within-person configurations of self-oriented, other-oriented, and socially prescribed perfectionism (SPP) in university students (n = 538) and adults with chronic illness (n = 773). Five unique configurations were found in both samples and three clusters replicated across samples. "Extreme perfectionists" with high scores across all perfectionism dimensions reported relatively poor physical health, psychological health, psychosocial resources, and well-being along with elevated neuroticism and conscientiousness. A group distinguished by elevated SPP also reported relatively poorer outcomes along with elevated neuroticism and lower conscientiousness. In contrast, "nonperfectionists" reported relatively elevated levels of health and well-being. These profiles differed in their links with health and well-being even after taking into account key differences in conscientiousness and neuroticism. Our results illustrate the importance of employing a person-oriented approach to the study of multidimensional perfectionism, especially as it relates to physical health, mental health, and subjective well-being.