This naturalistic study aims to evaluate the influence of antipsychotic treatment on the use of anticholinergics. The observed use of anticholinergics will give an indication of the occurrence of extrapyramidal side effects (EPS) in the different antipsychotic treatment conditions. The medication use of 1215 hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four antipsychotic treatment conditions are distinguished: 1) only first generation antipsychotics (FGA): patients receive one or a combination of first generation antipsychotics, 2) a combination of high potency FGA and second generation antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only SGA: patients receive one or a combination of SGA. Antipsychotic treatment significantly influences the use of anticholinergics. Anticholinergic use is highest in patients treated with high potency FGA (whether or not in combination with SGA) as compared with patients only treated with SGA and patients combining SGA with low potency FGA. The two latter groups do not significantly differ. However, there were no significant differences in the prevalence of EPS with the exception of akathisia between FGA and SGA. Thus, through the use of anticholinergics, EPS induced by FGA can be effectively reduced.