BACKGROUND: Although men who have sex with men (MSM) represent a dominant risk group for human immunodeficiency virus (HIV), the risk of HIV infection within this population is not uniform. The objective of this study was to develop and validate a score to estimate incident HIV infection risk. METHODS: Adult MSM who were tested for acute and early HIV (AEH) between 2008 and 2014 were retrospectively randomized 2:1 to a derivation and validation dataset, respectively. Using the derivation dataset, each predictor associated with an AEH outcome in the multivariate prediction model was assigned a point value that corresponded to its odds ratio. The score was validated on the validation dataset using C-statistics. RESULTS: Data collected at a single HIV testing encounter from 8326 unique MSM were analyzed, including 200 with AEH (2.4%). Four risk behavior variables were significantly associated with an AEH diagnosis (ie, incident infection) in multivariable analysis and were used to derive the San Diego Early Test (SDET) score: condomless receptive anal intercourse (CRAI) with an HIV-positive MSM (3 points), the combination of CRAI plus ≥5 male partners (3 points), ≥10 male partners (2 points), and diagnosis of bacterial sexually transmitted infection (2 points)-all as reported for the prior 12 months. The C-statistic for this risk score was >0.7 in both data sets. CONCLUSIONS: The SDET risk score may help to prioritize resources and target interventions, such as preexposure prophylaxis, to MSM at greatest risk of acquiring HIV infection. The SDET risk score is deployed as a freely available tool at http://sdet.ucsd.edu.