In the absence of controlled clinical trials, little is known about antipsychotic treatment in primary and secondary delusional parasitosis (DP). All available data on the efficacy of antipsychotics (APs) and the outcome in DP date back to the era of first-generation antipsychotics, whereas such data are lacking for second-generation antipsychotics (SGAs). To study outcome and efficacy of SGAs in all forms of DP by means of a case-based analysis, we extracted 63 cases from 434 available publications and assessed them by 2 independent raters using standardized criteria for efficacy and outcome. The time course of response and the SGA doses used in DP were also first studied. The sample was comparable to classic samples and comprised mainly secondary DP cases (56%). The median onset of effect occurred after 1.5 weeks, and the maximum effect occurred after 6 weeks (later in primary than secondary DP, 10 vs 3 weeks; P < 0.004). If a treatment of more than 8 weeks could be established, all cases responded at least partially. In the outcome analysis, partial or full remission was performed by 75% of cases (final outcome, therapy switches allowed). In the efficacy analysis, partial or full remission was reached in 69% of the situations when an SGA was introduced (without therapy switches). Secondary DP was more likely to respond to SGAs than primary DP (78% vs 59% trend). Risperidone and olanzapine were most widely used and resulted in full or partial remission in 69% and 72%, respectively. Doses were lower than those used in schizophrenia. This first retrospective case-based study provides low-level evidence that SGAs are effective in DP and that outcome is favorable, although a publication bias is likely. Our findings need to be confirmed by controlled trials.