Translocation t(4;14) is an independent prognostic factor for adverse outcome in multiple myeloma (MM). However, reports concerning the therapeutic effects of novel drugs on t(4;14) MM are few. We retrospectively investigated the clinical and prognostic significance of symptomatic MM cases with t(4;14) treated with novel therapies. Ninety-three patients (IgG, 56; IgA, 23; BjP, 14) newly diagnosed with MM were included (median age, 71 years; median observation period, 27.8 months). t(4;14) MM was diagnosed in 17 (IgG, 7; IgA, 9; BjP, 1) patients (18%). An association between t(4;14) and the IgA isotype was confirmed (p = 0.02). Overall survival (OS) at 3 years was lower in the t(4;14) patients than without t(4;14) group (81.2% vs 66.7%, p = 0.04). Multivariate analysis showed that t(4;14) was an independent predictor of OS (hazard ratio [HR], 7.58; 95.0% confidence interval [CI], 1.43–39.9; p = 0.0017). The ORR after autologous blood stem cell transplantation (ASCT) did not differ with or without t(4;14); progression-free survival tended to be prolonged in the group without t(4;14) (p = 0.088). Thus, even in the era of novel drugs, t(4;14) MM still has a poor prognosis, and triplet consolidation therapy should be continued.