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Smoking rates in schizophrenia are exceptionally high; however, cessation rates remain low with limited research on effective interventions. A critical component of intervention development is identifying the effects of abstinence that are most salient and therefore may contribute to lapse and relapse. We conducted a systematic review and meta-analysis of controlled laboratory studies investigating acute smoking abstinence effects among people with schizophrenia and schizoaffective disorder. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. OVID (MEDLINE, EMBASE, PsycINFO) and PubMed databases were searched from inception until November 2023. We identified (k = 16) articles meeting inclusion criteria; all assessed smoking abstinence (ranging 2–120 h). Acute abstinence resulted in large increases in reward-oriented craving and moderate increases in relief-oriented craving; these effects were greater in studies with longer abstinence duration (high certainty). We also observed significant increases in negative affect and global withdrawal symptoms, as well as memory disruption (moderate certainty). Qualitative synthesis suggests restlessness, irritability, anxiety, and visuospatial working memory may be additionally impacted. Findings with respect to negative symptoms and movement were mixed. Reward-oriented craving may constitute a key target of smoking cessation interventions for people with schizophrenia. In addition, identification of pharmacological and psychosocial interventions that address abstinence-induced changes in relief-oriented craving, memory, negative affect, restlessness, irritability, and anxiety may strengthen treatment outcomes. [ABSTRACT FROM AUTHOR]