Antipsychotic long-acting injections (LAIs) are often used in an attempt to improve medication adherence in people with schizophrenia. To compare first-generation antipsychotic long-acting injections (FGA-LAIs) with first- and second-generation oral antipsychotics in terms of clinical outcome. Systematic literature review. A meta-analysis of randomised controlled trials (RCTs) showed no difference in relapse or tolerability between oral antipsychotics and FGA-LAIs but global improvement was twice as likely with FGA-LAIs. Four prospective observational studies were identified; two studies reported lower discontinuation rates for FGA-LAIs compared with oral medication and two found that outcome was either no different or better with oral antipsychotics. Mirror-image studies consistently showed reduced in-patient days and admissions following a switch from oral antipsychotics to FGA-LAIs. The results are variable and inconclusive. Some evidence suggests that FGA-LAIs may improve outcome compared with oral antipsychotics. Methodological issues may partly explain the variable results. Selective recruitment in RCTs and lack of randomisation in observational studies are biases against LAIs, whereas regression to the mean in mirror-image studies favours LAIs. In terms of future research, a long-term pragmatic RCT of an FGA-LAI against an oral antipsychotic, in patients with problematic adherence, would be of value.