Background A beneficial effect of metformin on heart failure requires confirmation. Methods and Results Patients with new-onset type 2 diabetes mellitus during 1999 to 2005 were enrolled from Taiwan's National Health Insurance database and followed up from January 1, 2006, until December 31, 2011. Main analyses were conducted in an unmatched cohort (172 542 metformin ever users and 43 744 never users) and a propensity score matched-pair cohort (matched cohort I, 41 714 ever users and 41 714 never users). Hazard ratios were estimated by Cox hazard regression incorporated with the inverse probability of treatment weighting using the propensity score in the unmatched cohort and by naïve method in the matched cohort I. Results showed that the respective incidence rates of heart failure hospitalization in ever users and never users were 304.25 and 864.31 per 100 000 person-years in the unmatched cohort (hazard ratio, 0.350; 95% CI, 0.329-0.373) and were 469.66 and 817.01 per 100 000 person-years in the matched cohort I (hazard ratio, 0.571; 95% CI, 0.526-0.620). A dose-response pattern was consistently observed while estimating hazard ratios for the tertiles of cumulative duration of metformin therapy. Findings were supported by another propensity score-matched cohort created after excluding 10 potential instrumental variables in the estimation of propensity score (matched cohort II). An approximately 40% lower risk was consistently observed among ever users in different models derived from the matched cohorts I and II, but models from the matched cohort II were less subject to model misspecification. Conclusions Metformin use is associated with a lower risk of heart failure hospitalization.