We performed a systematic review and meta-analysis of randomized controlled trials comparing autologous hematopoietic cell transplantation (HCT) with other treatment modalities to analyze the risk for various secondary malignancies (SMs). Relative risks (RR) with 95% confidence intervals were estimated and pooled. Our search yielded 36 trials. The median follow-up was 55 (range 12-144) months. Overall, the RR for developing SMs was 1.23 ((0.97-1.55), I(2)=4%, 9870 patients). Subgroup analysis of trials assessing TBI-containing preparative regimens and of patients with baseline lymphoproliferative diseases, showed there was a higher risk for SMs in patients given autografts (RR=1.61 (1.05-2.48), I(2)=14%, 2218 patients and RR=1.62 (1.12-2.33), I(2)=22%, 3343 patients, respectively). Among all patients, there was a higher rate of myelodysplastic syndrome MDS/AML in patients given HCT compared with other treatments (RR=1.71 (1.18-2.48), I(2)=0%, 8778 patients). The risk of secondary solid malignancies was comparable in the short term between patients given HCT and patients given other treatments (RR=0.95 (0.67-1.32), I(2)=0%, 5925 patients). We conclude that overall the risk of secondary MDS/AML is higher in patients given autologous HCT compared with other treatments. In the subgroup of patients given a TBI-based regimen and in those with a baseline lymphoproliferative disease, there was a higher risk of overall SMs.