Cough associated with cancer or nonmalignant chronic disease is common and distressing. Levodropropizine, a peripherally acting drug, has been used as an alternative antitussive to opioids. The authors aimed to determine the efficacy and safety of levodropropizine in relieving cough associated with cancer or nonmalignant chronic disease. The authors searched five databases and hand searched relevant journals to identify randomized and nonrandomized controlled trials assessing the antitussive effect of levodropropizine for cough associated with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease, or chronic heart failure. Study quality was assessed using a modified version of the Centre for Reviews and Dissemination criteria. The search yielded 58 references. Six were checked in more detail, and four studies were included. Two were randomized controlled trials (RCTs) testing levodropropizine against dihydrocodeine and moguisteine, and two were nonrandomized placebo-controlled studies, all with important limitations and high risk of bias. Levodropropizine was significantly more effective than placebo in reducing cough frequency and severity, and equally effective as dihydrocodeine or moguisteine. It was generally well tolerated. The authors conclude that the evidence for the antitussive efficacy of levodropropizine in these patients is scarce, and is further limited by the methodological weaknesses of the primary studies. Further well-designed research is needed to support its use.