Background: Dentists, dental materials, and dental laboratories are exposed to different types of pathogenic microorganisms. Impression materials, impression trays, and poured stone cast have been said to be the main source of cross infection between patients and dentists. The aim of the present study consisted in evaluating the effectiveness of water washing and sodium hypochlorite disinfection in reducing the microbial load of alginate after mouth contact. Materials and Methods: In this in vitro experimental study twenty students voluntarily participated. The inclusion criteria were age between 21 and 24 years, and inexistence of systemic and salivary gland pathologies. For each participant, one impression was taken in alginate from the mandibular arch. These samples were submitted to water wash and sodium hypochlorite disinfection and to subsequent microbiological analysis. Statistical analysis included the analysis of variance for multiple comparisons (one-way ANOVA) followed by Student’s t-test. Results: After mouth contact, alginate microbial count increased from 1.72 ± 2.92 to 2.81 × 103 ± 5.36 × 102 CFU/mm2. It was seen that after water wash the microbial count decreased to 48.5% while after sodium hypochlorite disinfection the microbial count decreased to 99.99%. Conclusion: This study revealed that alginate impression can be effectively disinfected by sodium hypochlorite. Tap water rinsing reduces microbial load but does not eliminate the cross-infection potential of alginate impressions.