Background: Triplet therapies exert deeper responses and result in prolonged progression free survival (PFS) while the argument to favor doublets is their better toxicity profile. The objective of the current analysis is to test the hypothesis that triplets are tolerable, improve ≥ CR, ≥ VGPR, ORR rates and would translate to an improved PFS. Methods: We searched Pubmed, Cochrane databases and ASH, ASCO conference proceedings from 01/2000 through 01/2016 to identify the phase 3 RCTs that have randomized early relapsed myeloma patients ( ≤ 3 prior lines) to receive a triplet vs. doublet salvage regimen. A meta-analysis of 5 RCTs (PANORAMA1, MMVAR, ASPIRE, ELOQUENT2, TOURMALINE consisting of 3197 patients) was performed using the fixed (Mantel-Haenszel) and random (DerSimonain and Laird) models to calculate the impact of triplets versus doublets by evaluating the CR, ≥ VGPR, ORR, PFS and toxicities. Results: The pooled odds ratios of ORR, ≥ VGPR and ≥ CR with triplets vs. doublets were 1.811 (P< 0.000), 1.962 (P< 0.001), 2.325 (P< 0.000) respectively, indicating that the odds of achieving deeper responses are higher with triplets. The pooled hazard ratios (HR) for PFS was HR 0.674 (95% CI 0.613-0.741; P= 0.000) in favor of triplets. Q-statistic for PFS (P= 0.719; df= 4; I² = 0.00) suggests homogeneity across studies. Though the relative risk (RR) of selected ≥ grade 3 serious adverse events (G3 SAE) was higher with triplets (diarrhea, fatigue, thrombocytopenia 2.232, 1.654 and 2.161 respectively (P= 0.000), the overall G3 SAE were almost comparable with a RR 1.438 (P= 0.000), though favoring doublets. Conclusions: Our meta-analysis demonstrates that triplet regimens result in improved ORR, ≥ VGPR, ≥ CR and PFS compared to doublets. G3 SAEs are higher with triplets, however this appears to be influenced by the regimen-related toxicity from PANORAMA1 trial. Appropriate dose modifications or using selective HDAC inhibitors in future may mitigate the toxicities of the regimen. The pooled estimates of response and survival strongly favor triplets in the early relapsed setting.