Swine lagoon liquid may contain numerous pathogens at concentrations that are a risk to human health through on-farm contact or through off-farm exposure, such as may occur if the pathogens are transported to ground or surface water resources through seepage or spray irrigation. In this study, liquid samples were collected year-round from lagoons on four swine farms and analyzed for Salmonella and six microbial indicators of fecal contamination (fecal coliforms, E. coli, enterococci, Clostridium perfringens spores, somatic coliphages, and F-specific coliphages). Salmonella were measured at mean concentrations of 3.1 to 4.0 log(10) MPN/100 mL in untreated flushed swine waste, 2.2 to 2.4 log(10) MPN/100 mL in single-stage primary lagoon liquid, and 0.4 to 0.7 log(10) MPN/100 mL in the secondary lagoons of two-stage lagoon systems. Salmonella, fecal coliforms, E. coli, enterococci, somatic coliphages, and F-specific coliphages were reduced by 1 to 2 log(10) in single-stage lagoon systems, and by 2 to 3 log(10) in two-stage lagoon systems. C. perfringens spore reductions were significantly lower than for the other microbes analyzed in primary treatment lagoons (mean reductions = 0.6 to 0.8 log(10)), suggesting that effective removal of environmentally persistent pathogens such as helminths and protozoan parasites (e.g., Cryptosporidium parvum) may necessitate the use of two-stage lagoon systems, or alternative waste management techniques. Temperature was significantly associated with treatment efficacy for reductions of fecal coliforms and coliphages in at least one of the primary lagoons studied. In secondary lagoons, temperature was significantly associated with reductions of all the study microbes. Linear regression analysis of Salmonella reductions versus temperature in the secondary lagoons yielded an r(2) = 0.66. Based on statistical analysis of the magnitudes and correlations of their reductions, fecal coliforms and E. coli were determined to be the best microbial indicators of the reduction of Salmonella in swine waste lagoon systems. The results of this study indicate that single-stage, primary lagoons can substantially reduce concentrations of Salmonella, fecal coliforms, E. coli, enterococci, and coliphages in flushed swine waste, but were not effective for reducing concentrations of C. perfringens spores. Salmonella and other microbes can be further reduced in two-stage lagoon systems, yielding overall enteric microbe reductions that are more protective of public health.