Objective: Effective strategies are needed to encourage smoking cessation for smokers without an intention to quit. We systematically reviewed the literature to investigate whether smoking reduction therapy can increase the long-term cessation rates of smokers without an intention to quit. Methods: PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) on the effect of smoking reduction therapy on long-term smoking cessation in smokers without an intention to quit. The primary outcome was the cessation rate at the longest follow-up period. A random effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Results: Fourteen trials with a total of 7981 smokers were included. The pooled analysis suggested that reduction support plus medication significantly increased the long-term cessation of smokers without an intention to quit compared to reduction support plus placebo (RR, 1.97; 95% CI, 1.44–2.7; I 2, 52%) or no intervention (RR, 1.93; 95% CI, 1.41–2.64; I 2, 46%). In a subgroup of smokers who received varenicline or nicotine replacement therapy (NRT), the differences were also statistically significant. This suggests the safety of using NRT. The percentage of smokers with serious adverse events who discontinued because of these events in the non-NRT group was slightly significantly different than in the control group. Insufficient evidence is available to test the efficacy of reduction behavioural support in promoting long-term cessation among this population. Conclusions: The present meta-analysis indicated the efficacy of NRT- and varenicline-assisted reduction to achieve complete cessation among smokers without an intention to quit. Further evidence is needed to assess the efficacy and safety of reduction behavioural support and bupropion.