Insomnia is the most prevalent sleep disorder, affecting millions worldwide and taking a heavy toll on patient health with significant social and economic impact. Even though there are multiple different types of insomnia medications and behavioral therapies, there are still many individuals for whom treatment remains ineffective. The objective of this retrospective study was to analyze the effectiveness of daridorexant in a cohort of chronic insomnia patients largely transitioned from GABA-A positive allosteric modulators (benzodiazepines, zolpidem or eszopiclone) or other frequently prescribed insomnia medications (including trazodone, atypical antipsychotics or tricyclic antidepressants). A total of 86 patients were treated in the course of ordinary practice and the primary analytic endpoint was the change in Insomnia Severity Index (ISI) score following ≥ 30 nights of treatment with daridorexant. Results from 80 of the 86 patients with full data (65% female, mean age 53.5 years, 18.8% with comorbid obstructive sleep apnea, 91.3% transitioned from a different medication) showed a mean improvement in ISI score of 7.0 ± 0.54 points (SEM) (p < 0.0001) from 18.0 to 11.0. Overall, 78% of the cohort demonstrated a clinically meaningful improvement as defined by at least a six-point drop in ISI. Total sleep time increased by 54 ± 1.0 min (SEM) (p < 0.0001) from 6.0 h to 6.9 h. Mean sleep latency decreased by 23.9 ± 2.4 min (SEM) (p < 0.0001) from 58.8 min to 34.9 min. Wake after sleep onset decreased by 31.6 ± 3.2 min (SEM) (p < 0.001) from 42.8 min to 11.3 min. Sleep efficiency improved by 10.5 ± 1.1% (SEM) (p < 0.0001) from 79.3% to 89.8%. No significant adverse events were noted during the study duration. Keeping in mind this study’s limitations, these data suggest that for insomnia patients with an incomplete response to current therapy, switching to daridorexant is safe and may be an effective alternative treatment.