Background Laser excision is used routinely in the treatment of sarcoids but may be ineffective in cases where complete excision cannot be achieved. A multimodal approach is warranted in these cases. 5-FU may improve the lethal effect of cryotherapy as an adjunct to laser excision. Objectives To compare two treatment protocols for equine sarcoids: laser excision alone versus a combination protocol of laser excision, cryotherapy, and 5-FU chemotherapy. Factors associated with sarcoid recurrence are also investigated. Study Design Retrospective case controlled study. Results Eighty-four horses with 168 histologically confirmed sarcoids were included, with a median follow up time of 39 months (IQR 21-62 months). Sarcoid recurrence at the treated site was reported in 38% of cases and in 23% of any individual sarcoids. No significant difference was demonstrated between treatment categories in either rate of sarcoid recurrence (p=0.45 for any treated horse, p=0.63 for individual sarcoids) or time to sarcoid recurrence (p=0.73). Sarcoid recurrence was higher in horses with a greater number of sarcoids (OR 1.2 (1.0-1.5), p=0.03); when treatment had been received prior to admission (OR 7.6 (2.0-33), p=0.004); for individual sarcoids ≥100mm in diameter (OR 5.6 (1.1-30), p=0.03); and for treatment under general anaesthesia (OR 5.0 (1.4-19), p=0.01). Horses with urogenital sarcoids and >1 mixed sarcoid experienced more rapid recurrence (HR 3.6 (1.3-10), p=0.02 and HR 9.9 (3.3-30), p<0.001) and recurrence was less rapid following the treatment of a horse’s first sarcoid (HR 0.3 (0.1-0.7), p=0.009). Main Limitations Significant differences in case populations in each treatment category. Treatment selection was neither blinded nor randomised and missing data and recall bias limit the study’s power. Sarcoid recurrence was owner reported. Conclusions When assessing the likelihood of sarcoid recurrence, characteristics of the individual patient and sarcoid(s) are likely to be more significant than selection of any individual treatment protocol.