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Objective To determine the effectiveness of microsurgical testicular sperm extraction (micro-TESE) and intracytoplasmic sperm injection (ICSI) for men with Klinefelter syndrome (KS). Design Retrospective clinical study. Setting Private IVF center. Patient(s) Men with nonmosaic KS (n = 106), and men with nonobstructive azoospermia (NOA) and normal karyotypes (n = 379). Intervention(s) Micro-TESE on the day of oocyte retrieval. Main Outcome Measure(s) Sperm recovery, fertilization, pregnancy, and spontaneous abortion rates. Result(s) Sperm was successfully recovered in 50 of 106 (47%) men in the KS group and 188 of 379 (50%) in the NOA group. The fertilization rate was higher in the NOA group than the KS group (65% vs. 57%, respectively); however, pregnancy (55% vs. 53%) and abortion rates (12% vs. 11.5%) did not differ statistically significantly between groups. In the KS group, 23 pregnancies resulted in 29 live births; the 21 children who underwent genetic evaluation had normal karyotypes. Conclusion(s) Sperm recovery rates in men with KS were similar to those of men with NOA and normal karyotypes. The fertilization rate was statistically significantly lower for men with KS than men with NOA, but pregnancy and abortion rates were similar. We observed good sperm recovery and ICSI outcomes for patients with KS.