Background: Previous research that atypical antipsychotics were switched less often compared to typical antipsychotics, suggesting overall better treatment satisfaction. The objective of this study was to investigate the reasons for switching antipsychotics after initiating oral treatment with either typical or atypical antipsychotics in a clinical setting. Patients and Methods: A total of 123 patients that switched antipsychotic therapy were recruited from 17 psychiatric hospitals, of which 46 % switched because of lack of effect and 45 % because of adverse effects. Results: No significant differences were found between users of atypical versus typical antipsychotics in reasons for switching, both for overall adverse events, and lack of effect. In users of atypical antipsychotics extrapyramidal effects were reported less often as reason for switching (adjusted OR = 0.18 (95 % Cl = (0.07-0.51)). Patients on atypical antipsychotics switched more often because of weight gain (adjusted OR = 12.8 (95 % Cl = (1.50-109)). Conclusion: in conclusion, when switching occurred, no difference was found in the frequency of general tolerability or reported lack of effectiveness. However, the type of adverse event as a reason for switching differed between atypical and typical antipsychotics.