OBJECTIVE To assess 1-year persistence and adherence rates with drug therapy among patients with fibromyalgia (FM) and to identify factors associated with therapy discontinuation. METHODS This retrospective, cohort study included members ≥ 21 years old from the Maccabi Healthcare Services, a large health maintenance organization in Israel, who were diagnosed with FM from 2008 through 2011. Medications of interest included the anticonvulsant pregabalin, antidepressants [selective serotonin reuptake inhibitor (SSRI), serotonin/norepinephrine reuptake inhibitor (SNRI)], and tricyclic antidepressants (TCA). Time to treatment discontinuation and proportion of days covered (PDC) with FM-specific therapies during the year from first dispensed were analyzed. PDC < 20% was considered low adherence and PDC ≥ 80% was considered high adherence. Logistic regression models were constructed for multivariable analyses. RESULTS Overall, 3932 patients with FM were included; 88.7% were female. Pre-diagnosis use of medication of interest was documented in 41% of the study population. Of the remaining 2312 patients, 56.1% were issued a prescription, 45.0% were dispensed at least 1 medication in the year following diagnosis, and only 28.8% had prescriptions filled twice within the first year from diagnosis. Among newly prescribed patients, 1-year discontinuation was highest for TCA (91.0%) and lowest for SSRI/SNRI antidepressants (73.7%). Over half of the patients (60.5%) had fewer than 20% of the days covered by any medication during the year and only 9.3% were very adherent (PDC ≥ 80%). CONCLUSION This study clearly shows that in an Israeli "real-life" population of patients with FM, persistence and adherence with FM therapy in the year following diagnosis is remarkably low.