AIMS: To critically appraise the evidence for effectiveness of pharmacy-based needle/syringe exchange programs (Pharmacy-based NSPs) on risk behaviors (RBs), HIV/HCV prevalence, and economic outcomes among people who inject drugs (PWID). DESIGN: Systematic review and meta-analysis SETTING: PRIMARY CARE SETTING: PARTICIPANTS: Of 1,568 studies screened, 14 studies with N = 7035 PWID were included. MEASURES: PubMed, Embase, Web of Sciences, CENTRAL, and Cochrane review databases were searched without language restriction from their inception through January 27, 2016. All published study designs with control group that reported the effectiveness of Pharmacy-based NSP on outcomes of interest were included. Outcomes of interest are RB, HIV/HCV prevalence, and economic outcomes. The estimates of pooled effects of these outcomes were calculated as pooled odds ratio (OR) with 95% CI using a random-effects model. Heterogeneity was assessed by I2 and chi-squared tests. FINDINGS: Most studies (9/14, 64.3%) were rated as having a serious risk of bias, while 28.6% and 7.1% were rated as having a moderate risk and low risk of bias, respectively. For sharing-syringe behavior, Pharmacy-based NSPs were significantly better than no NSPs for both main (OR: 0.50 (95%CI = 0.34-0.73; I2 = 59.6%)) and sensitivity analyses, excluding studies with a serious risk of bias (OR: 0.52 (95%CI = 0.32-0.84; I2 = 41.4%)). For safe syringe disposal and HIV/HCV prevalence, the evidence for Pharmacy-based NSPs compared with other NSP or No NSP was unclear since few of the studies reported this and most of them had a serious risk of bias. Compared with the total lifetime cost of 55,640 USD for treating a person with HIV infection, the HIV prevalence among PWID has to be at least 0.8% (for Pharmacy-based NSPs) or 2.1% (for other NSPs) to result in cost-savings. CONCLUSIONS: Pharmacy-based needle/syringe exchange programs appear to be effective for reducing risk behaviors among people who inject drugs, though their effect on HIV/HCV prevalence and economic outcomes is unclear.