Dopamine D2-receptor blockade by antipsychotic medication reduces psychotic symptoms, but may reduce subjective well-being. The current study aims to further explore the relation between dopamine D2-receptor affinity and subjective well-being within a large sample of patients with psychotic disorders. Patients participated in a longitudinal naturalistic cohort study: the Genetic Risk and Outcome of Psychosis (GROUP) study. Three groups of antipsychotic medication were created on the basis of their affinity for the D2-receptor: (i) loose or partial agonistic binding, (ii) moderate binding, and (iii) tight binding. Subjective well-being was assessed using the Subjective Well-being under Neuroleptics scale (SWN) at baseline and the 3-year follow-up. In addition, we compared changes in SWN scores when switching to a more 'loose or partial agonistic' binding agent or to a 'tighter' binding agent between baseline and the 3-year follow-up. The final group included 388 patients at baseline and 290 at the 3-year follow-up. No significant differences in the SWN scores were found between the three affinity groups at baseline and the 3-year follow-up. In addition, analyses yielded no significant changes in SWN scores after switching to a more 'loose or partial agonistic' or more 'tight' binding antipsychotic agent. We did not find further support for the hypothesis that subjective well-being is associated with antipsychotics affinity for dopamine D2-receptors. This might imply that the effect of antipsychotic D2-receptors binding on subjective well-being is not large enough to be detected in this cross-sectional study. Other factors besides dopamine antagonism are probably more relevant for subjective well-being.