There is a high prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Antipsychotic treatment, especially duration and type of substance, is suspected to increase or even cause OCS. We examined in a naturalistic cross-sectional study the severity of OCS (Obsessive-Compulsive Inventory - Revised) and the incidence of obsessive-compulsive disorder (OCD) according to ICD-10 criteria in 70 patients with schizophrenia. 26 patients were treated with clozapine and 44 patients were treated with another second-generation antipsychotic (SGA). After group matching, the two groups did not differ significantly in age, gender, duration of illness, treatment duration with the current antipsychotic substance and chlorpromazine-equivalent dosage. Patients treated with Clozapine showed a significantly higher rate of OCD (χ = 7.304, p = 0.007) and a significantly higher severity of OCS (t = 2.216, p = 0.037) compared to patients treated with another SGA. For the whole sample, duration of treatment with the current antipsychotic medication correlated significantly (p = 0.033, r = 0.323) with the severity of OCS, controlled for duration of illness. However, there was no significant correlation between severity of OCS and duration of illness, controlled for duration of treatment with the current antipsychotic substance. Our data suggest an interrelation between the development of OCS or OCD and antipsychotic treatment, especially clozapine. Thereby, duration of treatment is correlated with the severity of OCS, irrespective of the duration of illness.