Study Design: Retrospective cohort study. Objectives: Reported incidences and complications of heterotopic ossification (HO) after using recombinant human bone morphogenetic protein–2 (rhBMP-2) in transforaminal lumbar interbody fusion (TLIF) have been inconclusive. This study was designed to evaluate both incidences of radiologic and symptomatic HO in a large series of TLIFs using rhBMP-2. Methods: A total of 996 disc levels in 927 consecutive TLIF patients were retrospectively evaluated at 6-month postoperative follow-up in a single surgical practice. Subjects were separated into the BMP group and the control group. Operative reports, pre- and postoperative medical records were reviewed. Computed tomography (CT) scans were analyzed and graded independently for ossification at each disc level of TLIF. Results: A total of 933 disc levels were in the BMP group, and 63 were in the control group. Six-month fusion rate of interbody was 92.5% in the BMP group, which was significantly higher in contrast to 71.4% in the control group ( P < .001). The incidence of radiologic HO in the BMP group was 13.5%, which was significantly higher than 1.6% in the control group ( P = .006). After controlling for basic demographics and comorbidities, the presence of radiologic HO was significantly associated with the use of rhBMP-2 ( P = .026). However, only one case in the BMP group (0.11%) developed a symptomatic HO (mild-medium left buttock pain, treated nonsurgically) involving left foramen of L5-S1. Conclusions: rhBMP-2 can be safely used in TLIF with regard to HO. There was a low rate of radiologic HO and minimal symptomatic HO, with high fusion rates at 6 months postoperative.