Swine manure is a valuable source of nitrogen, phosphorus and potassium. After solid-liquid separation, the resulting swine wastewater can be concentrated by reverse osmosis (RO) to produce a nitrogen-potassium rich fertilizer. However, swine wastewater has a high fouling potential and an efficient cleaning strategy is required. In this study, a semi-commercial farm scale RO spiral-wound membrane unit was fouled while processing larger volumes of swine wastewater during realistic cyclic operations over a 9-week period. Membrane cleaning was performed daily. Three different cleaning solutions, containing SDS, SDS+EDTA and NaOH were compared. About 99% of the fouling resistance could be removed by rinsing the membrane with water. Flux recoveries (FRs) above 98% were achieved for all the three cleaning solutions after cleaning. No significant differences in FR were found between the cleaning solutions. The NaOH solution thus is a good economical option for cleaning RO spiral-wound membranes fouled with swine wastewater. Soaking the membrane for 3 days in permeate water at the end of each week further improved the FR. Furthermore, a fouling resistance model for predicting the fouling rate, permeate flux decay and cleaning cycle periods based on processing time and swine wastewater conductivity was developed.