This retrospective study aimed to explore the relative efficacy and safety of different tacrolimus (TAC) concentrations in the treatment of patients with idiopathic membranous nephropathy (IMN). A total of 260 IMN patients with nephrotic syndrome (NS) were recruited. Among these, 125 patients had TAC concentrations no greater than 5 ng/ml (CTAC ≤ 5 ng/ml), and 135 patients had TAC concentrations greater than 5 ng/ml (CTAC > 5 ng/ml). The primary outcomes included complete remission (CR) rates and overall (OR) response rates. The secondary outcomes included 24-h urinary protein (24-h UP), serum albumin and serum creatinine, and adverse events (AEs). During the 12-month follow-up, the overall response rates were significantly different between the CTAC ≤ 5 ng/ml group and the CTAC > 5 ng/ml group (P < 0.0001). However, there was no significant difference in the CR at 12 months between the two groups (chi-square, 62% vs 63%, P = 0.852). Compared with the CTAC ≤ 5 ng/ml group, the CTAC > 5 ng/ml group had improved levels of 24 h UP (P = 0.017) and serum albumin (P = 0.010). Moreover, the incidences of acute reversible nephrotoxicity (P < 0.001), hepatotoxicity (P = 0.036), new-onset diabetes mellitus (P = 0.036), and glucose intolerance (P = 0.005) were lower in the CTAC ≤ 5 ng/ml group than in the CTAC > 5 ng/ml group. The CTAC > 5 ng/ml group was improved relative to the CTAC ≤ 5 ng/ml group in terms of a PR and CR at 6 months, but there was no difference in the CR between the two groups at 12 months.