Problem: Considerable amount of investigation has been carried out to study the effects of gelfoam in the middle ear mucosa. Most works are noncontrolled, controlled against not-intervened ears, or lack statistical analysis; moreover, we were unable to find investigations regarding its specific role on autologous prosthesis. Being biological materials, autologous prosthesis are susceptible to being affected by gelfoam in a manner not investigated up to now. Methods: Experimental autologous tympanoplasty was performed in guinea pigs bilaterally. Gelfoam was introduced in one of the ears intervened, while the control ear received the same surgical procedure, lacking the use of gelfoam. After an average of 11.6 weeks, temporal bones were harvested and histologically studied. We defined 7 parameters to be studied: avascular necrosis of the autologous prosthesis, adhesions and inflammation around the prosthesis, fibrosis in middle ear space, bone formation, adhesions of the tympanic membrane, and foreign-body reaction focuses. Results: Eighteen adult guinea pigs were operated on; 8 animals died before examination time was achieved. Results from the remaining 10 revealed a tendency of worst scores in the gelfoam group for the majority of the parameters tested, with statistical significance for adhesions of the ossicular chain and foreign-body reaction focuses ( P < 0.05). Nevertheless, the gelfoam group presented better results regarding avascular necrosis than the control group (without statistical significance). Conclusion: We demonstrated that gelfoam negatively affects anatomical results of ossiculoplasty, but at the same time we could observe that the reaction gelfoam generates inside the middle ear protects the autologous prosthesis against avascular necrosis. We theorize that the same chronic inflammatory reaction may provide better conditions for autologous prosthesis survival. Significance: This result represents a dilemma for the surgeon, because gelfoam may have deleterious and, at the same time, beneficial effects on the results of autologous ossiculoplasty. Support: This investigation was supported by the special funds for residents research projects of the Pontificia Universidad Católica de Chile, 2002.