To study outcome determinants of schistosomal periportal thickening/fibrosis (PPT/F), 199 subjects (mean age = 24.0 years, range = 7-68 years), 109 with mild (image pattern C) PPT/F, 69 with moderate (image pattern D) PPT/F, and 21 with severe (image patterns E and F) PPT/F were treated with praziquantel and evaluated every six months for a mean duration of 26 months. Subjects excreting Schistosoma mansoni eggs during any of the six-month evaluations were offered repeat treatment. Thirty-five had some improvement, and 69 had total resolution of PPT/F, of which 63.8% resolved within one year. Compared with subjects with moderate lesions, a significantly higher proportion of subjects with mild lesions had resolution/improvement of PPT/F (40.6% versus 69.7%, P < 0.001). Subjects with severe PPT/F showed no improvement. Resolution of PPT/F was significantly more frequent at a younger age, among seronegative for hepatitis B virus and among those with a lower frequency of post-treatment recurrence of S. mansoni infections.