Background: Insomnia is common in primary care, can persist after co-morbid conditions are treated, and may require long-term medication treatment. A potential alternative to medications is cognitive behavioral therapy for insomnia (CBT-I). Methods: In accordance with PRISMA guidelines, we systematically reviewed MEDLINE, EMBASE, the Cochrane Central Register, and PsycINFO for randomized controlled trials (RCTs) comparing CBT-I to any prescription or nonprescription medication in patients with primary or comorbid insomnia. Trials had to report quantitative sleep outcomes (e.g. sleep latency) in order to be included in the analysis. Extracted results included quantitative sleep outcomes, as well as psychological outcomes and adverse effects when available. Evidence base quality was assessed using GRADE. Results: Five studies met criteria for analysis. Low to moderate grade evidence suggests CBT-I has superior effectiveness to benzodiazepine and non-benzodiazepine drugs in the long term, while very low grade evidence suggests benzodiazepines are more effective in the short term. Very low grade evidence supports use of CBT-I to improve psychological outcomes. Conclusions: CBT-I is effective for treating insomnia when compared with medications, and its effects may be more durable than medications. Primary care providers should consider CBT-I as a first-line treatment option for insomnia. Keywords: Insomnia, Sleep, Behavior therapy, Cognitive therapy, Hypnotics and sedatives