Since its original description in 1982, transforaminal lumbar interbody fusion (TLIF) has grown in popularity as a means for achieving circumferential fusion. The authors sought to define the perioperative complication rates of the TLIF procedure at a large academic medical center. For all eligible patients from a consecutive series of 531 TLIF procedures, the institution's complication database and the medical record were reviewed to identify complications. Medical, nonprocedure-related complications such as myocardial infarction and pulmonary embolism were excluded due to inconsistency in the recording of these complications in the database. Rates were calculated for each type of complication, and subgroup analysis was performed to investigate the effect of previous lumbar surgery, and of multilevel versus single-level interbody fusion on complication rates. Odds ratios were calculated and evaluated using chi-square analysis. Five hundred thirty-one patients underwent a TLIF procedure during the study period. Two hundred forty-four patients (46%) had undergone a previous lumbar operation. Interbody fusion was performed at 1 level in 317 patients, at 2 levels in 188 patients, at 3 levels in 24 patients, and at 4 levels in 2 patients. One hundred thirty-five patients (25.4%) had at least one procedure-related complication. The most common complications were durotomy (14.3% of patients) and infection (3.8% of patients). Symptomatic screw misplacement (2.1% of patients) and interbody cage migration (1.8% of patients) were less common complications. The overall complication rate was greater in those patients who had undergone a previous operation (OR 1.75, 95% CI 1.18-2.59; p < 0.01) and in those who had multilevel surgery (OR 1.54, 95 % CI 1.04-2.28; p = 0.03), and the incidence of durotomy was higher in patients who had a previous operation (OR 1.75, 95% CI 1.07-2.87; p = 0.03). These differences were statistically significant. Durotomy also occurred more frequently in patients who had multilevel interbody fusion (OR 1.49, 95% CI 0.92-2.43; p = 0.13). A trend toward higher infection rates in those patients who underwent multilevel interbody fusion was observed (OR 1.5, 95% CI 0.62-3.68; p = 0.49), but this was not statistically significant. Infection rates did not differ between revision and first-time surgeries. Transforaminal lumbar interbody fusion has gained widespread popularity as a procedure for achieving arthrodesis in the lumbar spine. Complications occurred more often in patients undergoing revision surgery or multilevel interbody fusion. Durotomy and infection were the most common complications in this series.