ImportanceIn individuals with schizophrenia, antipsychotic-induced dysfunctions are frequent but often underexplored in clinical practice.ObjectiveTo synthetize the data of observational studies exploring the prevalence of sexual dysfunction in individuals with schizophrenia-spectrum disorders as well as associated factors.Data SourcesA systematic literature search without language or time restrictions was conducted in Google, Google Scholar, PubMed/MEDLINE, Science Direct, and Université Sorbonne Paris Cité for studies published up to June 8, 2022.Study SelectionAll observational studies reporting a prevalence of sexual dysfunction in schizophrenia-spectrum disorder were included.Data Extraction and SynthesisThe MOOSE guidelines with independent extraction by 2 observers and random-effects models were used.Main Outcomes and MeasuresThe prevalence of sexual dysfunction and each specific dysfunction.ResultsA total of 72 of 1119 studies from 33 countries on 6 continents published from inception to June 2022 were included with a total of 21 076 participants with schizophrenia. The pooled global prevalence of sexual dysfunctions was 56.4% (95% CI, 50.5-62.2), with a prevalence of 55.7% (95% CI, 48.1-63.1) for men and 60.0% (95% CI, 48.0-70.8) for women. The most frequent sexual dysfunction was erectile dysfunction in men (44%; 95% CI, 33.5-55.2), followed by loss of libido in men (41%; 95% CI, 30.7-51.4), ejaculation dysfunction in men (39%; 95% CI, 26.8-51.8), orgasm dysfunction in women (28%; 95% CI, 18.4-40.2), and amenorrhea in women (25%; 95% CI, 17.3-35.0). Factors associated with heterogeneity were study design, time and location, sociodemographic data, alcohol use disorder, psychiatric diagnosis, illness severity, and the use of antidepressants and anxiolytics. Sexual dysfunctions were more frequent in schizophrenia vs schizoaffective disorders, and erectile disorders were less frequent in individuals with longer illness duration. Antidepressant and mood stabilizer prescriptions were associated with lower rates of erection disorders (β, −6.30; 95% CI, −10.82 to −1.78); P = .006 and −13.21; 95% CI, −17.59 to −8.83; P < .001, respectively) and ejaculation disorders (β, −6.10; 95% CI, −10.68 to −1.53; P = .009 and β, −11.57; 95% CI, −16.34 to −6.80; P < .001, respectively). No obvious improvements in the rates of sexual dysfunction at other times were found, and there were conflicting results regarding antipsychotic classes.Conclusions and RelevanceThis systematic review and meta-analysis found a high prevalence of sexual dysfunction among individuals with schizophrenia, with considerable heterogeneity in associated factors. The findings also suggest that some dysfunctions may be explained by schizophrenia. The association between lower rates of dysfunction and antidepressant use suggests that treating comorbid depression could be an effective strategy to improve sexual health. A lack of data on metabolic parameters and physical health in general was also noted, while these issues are frequent in the care of schizophrenia.