Healthcare-associated pneumonia (HCAP) may have a more severe course than community-acquired pneumonia (CAP); hence, it is more likely to be caused by drug-resistant bacterial pathogens and anaerobes involved in aspiration pneumonia. We compared the efficacy and safety of initial empiric therapy with piperacillin/tazobactam (PIPC/TAZ, 13.5 g/day) with that of meropenem (MEPM, 1.5 g/day) as single broad-spectrum regimens with gram-negative and anaerobic coverage in patients with HCAP in Japan. The clinical cure rate was 75.9 % (22/29 cases) in the PIPC/TAZ group and 64.3 % (18/28 cases) in the MEPM group. The clinical efficacy rate was 87.9 % (29/33 cases) in the PIPC/TAZ group and 74.2 % (23/31 cases) in the MEPM group. The bacteriological eradication rate was 94.4 % (17/18) in the PIPC/TAZ group and 87.5 % (14/16) in the MEPM group. Adverse drug reactions were seen in 22.4 % (11/49 cases) of patients in the PIPC/TAZ group and 17.4 % (8/46 cases) of patients in the MEPM group. Although not statistically different, the PIPC/TAZ group had a slightly higher efficacy rate than the MEPM group. Both treatment regimens are tolerable and might be appropriate to use as initial empiric therapy for HCAP in Japan. To investigate the differences in efficacy profiles of those two regimens, a further confirmatory study with a larger cohort as determined by a power analysis is recommended.