Continuous exposure to schistosome-infested water results in acute and chronic morbidity in all ages. We analysed occurence of organomegaly via ultrasonography and investigated a possible additive effect of dual-dose drug administration in 401 Schistosoma haematobium infected individuals from a highly endemic area in Mali. Mean intensity of infection at baseline (22.0 eggs per 10 ml) was reduced to 0.22 eggs per 10 ml 9 weeks after treatment (both treatments combined). Odds of persistent infection among those given dual-dose treatment was 41% of that in people given single dose (b = 0.41; p = 0.05; 95% CI 0.17–1.00), but after two years, 70.7% of the 157 participants, who completed the survey, were re-infected with no significant difference in prevalence and intensity of infection between treatment groups. Resolution of organomegaly occurred in all age groups after treatment. A novel association between Schistosoma haematobium infection and moderate portal vein enlargement was found in 35% (n: 55). Severe portal vein diameter enlargement was found in 3.2%. After two years, moderate hepatomegaly was present in 50.6%, moderate splenomegaly in 45.6% and moderate portal vein diameter enlargement in 19%. A subsequent dose of PZQ did not provide any additional long-term advantages.