Cognitive behavioral therapy for insomnia (CBT-I) is effective for treatment of primary insomnia. There has been no synthesis of studies quantifying this effect on insomnia comorbid with medical and psychiatric disorders using rigorous selection criteria. The objective of this study was to quantify the effect of CBT-I in studies including patients with medical or psychiatric disorders. Studies were identified from 1985 through February 2014 using multiple databases and bibliography searches. Inclusion was limited to randomized controlled trials of CBT-I in adult patients with insomnia diagnosed using standardized criteria, who additionally had a comorbid medical or psychiatric condition. Twenty-three studies including 1379 patients met inclusion criteria. Based on weighted mean differences, CBT-I improved subjective sleep quality post-treatment, with large treatment effects for the insomnia severity index and Pittsburgh sleep quality index. Sleep diaries showed a 20 min reduction in sleep onset latency and wake after sleep onset, 17 min improvement in total sleep time, and 9% improvement in sleep efficiency post-treatment, similar to findings of meta-analyses of CBT-I in older adults. Treatment effects were durable up to 18 mo. Results of actigraphy were similar to but of smaller magnitude than subjective measures. CBT-I is an effective, durable treatment for comorbid insomnia.