This study examined objective quality of life (work, academic success, living situation, relationships, support system) and subjective quality of life (Sense of Coherence and Short-Form Health Survey-36) in an adult sample of males (n = 50, mean age: 30 years) with Asperger syndrome diagnosed in childhood and followed prospectively over two decades. The association between long-term diagnostic stability of an autism spectrum disorder and/or comorbid psychiatric disorders with quality of life was also examined. The results showed great variability as regards quality of life. The subsample that no longer fulfilled an autism spectrum disorder had full-time jobs or studies (10/11), independent living (100%), and reported having two or more friends (100%). In the stable autism spectrum disorder group, 41% had full-time job or studies, 51% lived independently, and 33% reported two or more friends, and a significant minority had specialized employments, lived with support from the government, or had no friends. Academic success was positively correlated with IQ. A majority of the total group scored average Sense of Coherence scores, and the mean for Short-Form Health Survey-36 was above average regarding psychical health and below average regarding mental health. Stability of autism spectrum disorder diagnosis was associated with objective but not subjective quality of life, while psychiatric comorbidity was associated with subjective but not objective quality of life.