OBJECTIVES: To examine medication adherence and discontinuation in patients with bipolar disorder (BP) initiating a long acting injectable antipsychotic (LAI) versus those who changed to a different oral antipsychotic. METHODS: This retrospective cohort analysis used Truven Health Analytics MarketScan® Commercial and Medicaid claims databases. Of the adult patients (≥18 years) diagnosed with BP, two mutually exclusive cohorts were created: LAI cohort, defined as initiating an LAI (no prior LAI therapy) between 01/01/2013 and 06/30/2014; and oral cohort, defined as patients who changed to a different oral antipsychotic (mono-therapy) during the same period. The first day of initiating an LAI or changing oral antipsychotic was the index date. Linear and Cox regression models were conducted to estimate medication adherence (proportion of days covered (PDC)) and time to medication discontinuation (continuous medication gap ≥ 60 days), respectively. Models adjusted for patient demographic and clinical characteristics, baseline medication use, and baseline ED or hospitalizations. RESULTS: The final sample consisted of 1,672 (14.7%) LAI initiators and 9,672 (85.3%) oral antipsychotic users. Compared with the oral cohort, LAI initiators had better medication adherence (PDC≥0.8: 30.9% vs. 21.5%, p<0.001; unadjusted mean: 0.51 vs.0.45; p<0.001). Controlling for covariates, the adjusted mean of PDC remained higher in the LAI initiators than in the oral cohort (0.50 vs. 0.45; p<0.001). Additionally, LAI initiators had a lower discontinuation rate (76.5% vs. 82.4%; p<0.001) and a significantly longer time to medication discontinuation than the oral cohort. The median time to discontinue index LAI was 149 days, compared with 99 days for oral monotherapy (p<0.001). The oral cohort had a higher hazard than the LAI cohort for discontinuing their index treatments (hazard ratio: 1.19; p<0.001). CONCLUSIONS: This real-world study suggests that patients with BP initiating LAIs had better medication adherence and lower discontinuation risk than those who changed to different oral antipsychotic monotherapy.