Our aim was to study the risk of developing tardive dyskinesia in highly vulnerable patients (i.e., middle-aged and older adults with borderline dyskinesia) treated with conventional versus atypical antipsychotics.We examined the cumulative incidence of definitive tardive dyskinesia at 1, 3, and 6 months during antipsychotic treatment among 240 outpatients at least 45 years of age who had borderline tardive dyskinesia at baseline. Patients treated with conventional antipsychotics were approximately two times more likely to develop definitive tardive dyskinesia during the study period compared with those treated with atypical antipsychotics (p <.001). This difference was found despite patients in the atypical antipsychotic group being significantly older and having more severe extrapyramidal symptoms at baseline than those prescribed typical antipsychotics. Among patients at a very high risk for worsening tardive dyskinesia, the use of atypical antipsychotics was associated with a significantly lower risk of developing definitive tardive dyskinesia compared with conventional antipsychotics.