Little is known about the role of psychopharmacological treatment and course of illness in patients diagnosed with a paranoid personality disorder. This short communication provides a naturalistic study of a psychiatric hospital case series. Fifteen consecutive patients were retrospectively studied. The Clinical Global Impression was rated at first admission, at last psychiatric contact, and after a 6-week observation period with or without antipsychotic treatment. During psychiatric admissions, three patients improved markedly, eight showed only minor changes, and four worsened. In total, seven patients had been administered any antipsychotic medication. The median duration of treatment was 15 weeks (range 4 days–328 weeks). No major adverse effects were noted. Among patients with sixth-week observations available, four had received antipsychotics; they appeared to improve considerably compared with six patients who had not received antipsychotics. Although the findings should be interpreted with caution, they support the notion of the disorder being a relatively chronic condition, although antipsychotics appeared to be safe and possibly had an effect in the short term.