Background: There is lack of studies exploring the incidence and association with diseases of the S1S2S3 electrocardiogram (ECG) pattern in the general population. Subjects and methods: This population study included 6299 individuals aged 30+, and explored the prevalence and association between S1S2S3 and cardiovascular and pulmonary diseases. Criteria for the S1S2S3-I and S1S2S3-II ECG pattern were fulfilled when there was an S wave in the leads I, II and III, and the S-wave amplitude was greater than the R-wave amplitude in one or two of the leads, respectively. Results: The S1S2S3-I ECG pattern was found in 2332 subjects (36.9%). After age adjustment, hypertension was associated with S1S2S3-I (Odds ratio [OR] 1.25, 95% CI 1.12–1.41, p < 0.001). This age-adjusted association was statistically significant among men but not among women (OR 1.37, 1.16–1.62, p < 0.001 and OR 1.13, 0.97–1.33, p = 0.126, respectively). The S1S2S3-II ECG pattern was present in 193 subjects (3.1%). After age adjustment, heart failure proved to be associated with S1S2S3-II (OR 1.85, 1.18–2.90, p = 0.007). Dividing the population by sex, resulted in a statistically significant age-adjusted association for men but not for women (OR 2.30, 1.22–4.33, p = 0.010 and OR 1.59, 0.83–3.03, p = 0.159, respectively). Interactions with sex were statistically non-significant. Conclusion: In the general adult population, the prevalence of the S1S2S3 ECG pattern is markedly affected by the diagnostic ECG criteria. The S1S2S3-I pattern was associated with hypertension, while S1S2S3-II was associated with heart failure, and both associations were enhanced in men. The associations with other studied cardiovascular and pulmonary diseases were minor and not clinically useful for risk stratification.