Blood donors attending a donation session may be deferred from donating blood due to a failure to meet low hemoglobin (Hb) thresholds. This costs the blood donor service and donors valuable time and resources. In addition, donors who are deferred may have more symptoms, and as a direct and/or indirect effect of their experience, return rates of donors deferred for low Hb are reduced, even in repeat donors. It is therefore vital that low Hb deferral (LHD) is minimized. The aim of this updated systematic review is to expand the evidence base for factors which affect a donor's risk of deferral due to low Hb. Studies were identified by searching MEDLINE, Embase, The Cochrane Library, and the WHO International Clinical Trials Registry to March 2019. Demographic data, donor history, hematological/biological factors, and the primary outcome of deferral due to low Hb were extracted. Our primary outcome was deferral due to low Hb. Analyses were descriptive and quantitative; pooled odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by meta-analysis using random-effects models. A total of 116 studies met the inclusion criteria. Meta-analysis showed a significantly greater risk of LHD in females compared with males in studies applying universal Hb thresholds for males and females (OR 14.62 95% CI 12.43-17.19) and in those which used sex-specific thresholds (OR 5.73, 95% CI 4.36-7.53). Higher rates of LHD were also associated with increasing age in men, low body weight, shorter interdonation interval, donors of Hispanic or African descent, higher ambient temperature, donors with low ferritin levels, and donation in a fixed donor center. There was conflicting evidence on the effect of new and repeat donor status, and blood group. This work has strengthened the evidence of the previous review in identifying factors that should be considered in studies of donor deferral and highlighting areas in need of further study, including ABO and Rh blood groups, previous platelet donation, diet, smoking, time of day, and genetic data. These factors may lead to individually tailored donation criteria for safe and efficient donation in the future. •Evidence from 116 studies identifies factors associated with low hemoglobin deferral.•Risk of deferral increased in older male donors and those with lower body weight.•Hispanic or African donors at greater risk of deferral than white donors.•Higher risk of deferral occurs with shorter interval between blood donations.•Higher ambient temperature and donation site increase the risk of deferral.•Further evidence required for smoking, diet, blood group, and genetic factors.