Subcutaneous testosterone (T) pellets are a viable treatment modality for hypogonadism. Optimal dosing, frequency of reimplantation, and long-term safety of T pellets remain incompletely elucidated parameters. A retrospective review of 273 patients treated for hypogonadism using subcutaneous T pellets was performed. Serum total T (TT), free T (FT), and estradiol (E2) levels were analyzed as a function of time from implantation, number of pellets implanted (6-9 or 10-12), body mass index (BMI; <25 or ≥ 25 kg/m(2)), number of implantations (≤ 4 rounds, 501 insertions), and preimplantation T levels (<300 or ≥ 300 ng/dL). T decay was determined using linear regression and TT levels immediately postimplantation and the time for TT levels to reach 300 ng/dL extrapolated for all variables. Mean patient age ± SD was 56 ± 12.6 years. Baseline TT level was 328 ± 202 ng/dL, FT 9.49 ± 27.8 pg/mL, and E2 25.1 ± 17.3 pg/mL. Extrapolated TT and FT peaks were lower in men receiving 6 to 9 pellets than men receiving 10 to 12, although decay rates differed insignificantly. E2 levels rose significantly in men receiving 10 to 12 but not 6 to 9 pellets. Men with BMI ≥ 25 kg/m(2) attained lower TT peaks with slower decay than men with BMI <25 kg/m(2) receiving 10 to 12 pellets, although 300 ng/dL TT levels were reached at approximately 100 days in both groups. No differences were seen in decay rates for men with multiple implant rounds, and no differences in T peaks or decay rates were seen in men with preimplant T level <300 or ≥ 300 ng/dL. One patient developed erythrocytosis, and no prostate-specific antigen recurrences were observed in men with prostate cancer treated with T pellets. Men with BMI <25 kg/m(2) should receive fewer pellets, and reimplantation for all men should occur 100 to 120 days after prior implantation. Men receiving 10 to 12 pellets have higher E2 levels, potentially reflecting increased aromatization of T. Reimplantation and preimplantation TT levels do not affect pellet decay kinetics.