Use of concomitant medications with antipsychotic agents in the treatment of schizophrenia is common but lacks a clear scientific rationale. We evaluated concomitant medication usage during the first 6 months of the prospective, observational, European Schizophrenia Outpatient Health Outcomes (SOHO) study, examining its frequency, variation according to type of antipsychotic drug used, and impact on treatment tolerability. We also determined factors that were associated with concomitant medication use. The use of concomitant medications differed greatly among the countries participating in the SOHO study. The presence of depressive symptoms and being female were associated with the use of concomitant antidepressants. Certain antipsychotics were associated with less use of concomitant medications: significantly fewer olanzapine-, quetiapine- and clozapine-treated patients used concomitant anticholinergics or anxiolytics/hypnotics. Patients using concomitant medications had an increased incidence of sexually related side effects and extrapyramidal side effects (EPS) at 6 months follow-up compared with patients not using concomitant medications. The results should be interpreted conservatively due to the observational design of SOHO.