Blooms of Dinophysis ovum and Mesodinium spp. have been observed in the Gulf of Mexico since 2007 using the Imaging FlowCytobot technology. Bloom dynamics of these two organisms in conjunction with ancillary environmental data for a 5-year period were analyzed to identify the conditions necessary for bloom initiation or presence with the goal of predicting future blooms of D. ovum. Using time-series analysis, we observed a positive time-lagged correlation between the two organisms in each year when both were present, which suggests that the presence of Mesodinium may be useful as a leading indicator for a D. ovum bloom. Although in some cases D. ovum and Mesodinium co-occurred, no strong predator–prey relationship was observed. We identified a narrow range of temperature and salinity that could be necessary for bloom initiation of D. ovum and Mesodinium in the Gulf of Mexico. Analysis of images over the time series revealed a wide range in the size of Mesodinium cells, which suggests that species other than M. rubrum may be present in the Gulf of Mexico. Based on the occurrence of a D. ovum bloom preceded by low abundances of Mesodinium, we suggest that D. ovum is able to utilize ciliates other than M. rubrum as prey. Our observations indicate that environmental conditions, as well as Mesodinium abundance and species composition, can affect initiation, presence or abundance of D. ovum and thus may help in the prediction of future blooms.